Iaoe?iiaeueia AEAAeAI?ss IAOE OE?A?IE

?INOEOOO A?IO?I?? ?i. I.A.Iaeeaae?ia

Neiii?ianueea-I?ieaie?o

Ieaia A?eoi??aia

OAeE 577.112:577.151.6

Aoaeoi?ia ae?y o?a?eiiaaio/o?a?eio oa ?o o?aaiaio?a

ia aeanoeaino? Glu-ieaci?iiaaio

03.00.04 — A?io?i?y

Aaoi?aoa?ao

aeena?oaoe?? ia caeiaoooy

iaoeiaiai nooiaiy eaiaeeaeaoa

a?ieia?/ieo iaoe

Ee?a 1999 Aeena?oaoe??th ? ?oeiien.

?iaioa aeeiiaia a ?inoeooo? a?io?i?? ?i.I.A.Iaeeaae?ia IAI Oe?a?ie

Iaoeiaee ea??aiee – aeieoi? a?ieia?/ieo iaoe, i?ioani?

Eoae?iia Noai?neaa Ieaenaiae?iae/,

?inoeooo a?io?i?? ?i.I.A.Iaeeaae?ia IAI Oe?a?ie,

caa?aeoaa/ a?aeae?eo o?i?? oa a?io?i?? oa?iaio?a.

Io?oe?ei? iiiiaioe: aeieoi? a?ieia?/ieo iaoe, i?ioani?

Aa?aia?iei Eocueia Ieeeoiae/,

Ee?anueeee iaoeiai-aeine?aeiee ?inoeooo ioiea?eiaieia??
?i.I.N.Eieii?e/aiea IIC Oe?a?ie,

aieiaiee iaoeiaee ni?a?ia?oiee;

aeieoi? a?ieia?/ieo iaoe, i?ioani?

E?a???a Aieiaeeie? Einoyioeiiae/,

?inoeooo a?ii?aai?/ii? o?i?? oa iaooio?i?? IAI Oe?a?ie,

caa?aeoaa/ a?aeae?eo o?i?? a?ee?a.

I?ia?aeia onoaiiaa – Ee?anueeee oi?aa?noeoao ?iai? Oa?ana Oaa/aiea

(eaoaae?a a?io?i??) I?iina?oe Oe?a?ie, i.Ee?a.

Caoeno a?aeaoaeaoueny “ 27 ” aa?aniy 1999 ?. i 14 aiaeei? ia can?aeaii?
niaoe?ae?ciaaii? a/aii? ?aaee Ae 26.240.01 a ?inoeooo? a?io?i??
?i.I.A.Iaeeaae?ia IAI Oe?a?ie (252601, Ee?a-30, aoe.Eaiioiae/a, 9).

C aeena?oaoe??th iiaeia iciaeiieoenue o a?ae?ioaoe? ?inoeoooo a?io?i??
?i.I.A.Iaeeaae?ia IAI Oe?a?ie (252601, Ee?a-30, aoe.Eaiioiae/a, 9).

Aaoi?aoa?ao ?ic?neaiee “26” na?iiy 1999 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? a/aii? ?aaee

eaiaeeaeao a?ieia?/ieo iaoe e??naiei i.a. Caaaeueia oa?aeoa?enoeea
?iaioe

Aeooaeuei?noue oaie. Oa?iaioaoeaia ?icuaieaiiy o?a?eiiaiai caonoea –
o?a?eiie?c – ? iaeiei c iaoai?ci?a, ui caaacia/othoue i?aeo?eiaiiy
??aeeiai noaio e?ia? a i?aai?ci?. O ii?i? i?ae o?a?eiie?oe/ith nenoaiith
oa nenoaiith cn?aeaiiy e?ia? ?nio? ??aiiaaaa. C ?? ii?ooaiiyi
aaciina?aaeiuei iia’ycai? ??ciiiai?oi? na?oeaai-noaeeii? caoai?thaaiiy,
o?iiaice oa aaii?aa??. O?a?eiie?oe/ia nenoaia aeeth/a? iaaeoeaiee
i?ioa?iaio ieaci?iiaai, yeee aeoeao?oueny aei ieaci?io (EO 3.4.21.7),
caeaoiiai a?ae?ie?coaaoe o?a?ei aei ?ic/eiieo i?iaeoeo?a. Ooieoe?th
aeoeaaoe?? ieaci?iiaaio ca o?c?ieia?/ieo oiia aeeiiothoue oeaieiiee
aeoeaaoi? ieaci?iiaaio (t-PA) oa aeoeaaoi? o?ie?iaciiai oeio. Ca
?nioth/ith oai???th, iniiaith iieaeoey?iiai iaoai?cio o?a?eiie?co ?
ooai?aiiy iio??eiiai eiiieaeno: oeaieiiee aeoeaaoi?
ieaci?iiaaio–ieaci?iiaai–o?a?ei. Ia o?a?ei? a?aeaoaathoueny eeth/ia?
i?ioeane o?a?eiie?co. Caiaeii aeoeaiee oa?iaio aea?eueiy?oueny o
e?iaioie, aea oaeaeei ? iaiai?ioii ?iaeoeao?oueny i?e?iaeieie
?ia?a?oi?aie – (2-aioeieaci?iii oa (2-iae?iaeiaoe?iii. ?nioth/a
iieaeoey?ia iiaeaeue o?a?eiie?co aaco?oueny caeaa?eueoiai ia
a?eie-a?eeiaeo aca?iiae?yo, oiaoi iaiao?aeia ni?aoe?y ieaci?iiaaio ia
o?a?ei? oa, ye iane?aeie oeueiai, aeoeaaoe?y i?ioa?iaioo.

Oaea iiiaae o?eaeoeyoue ?ie?a aeine?aeaeothoue eiioi?iaoe?ei? ci?ie, ye?
a?aeaoaathoueny o neeaaeiii?aai?ciaai?e iieaeoe? ieaci?iiaaio i?e
aca?iiae?? c iecueeiiieaeoey?ieie e?aaiaeaie, ui aeyaey?oueny a
?iceiiia?oaaii? aioo??oiueiiieaeoey?ieo ca’yce?a, i?eoaiaiieo iieaeoe?
ieaci?iiaaio. Oae? eiioi?iaoe?ei? ia?aoiaee aaaeeea? aeey aeeiiaiiy
i?ioa?iaioii eiai iniiaii? o?c?ieia?/ii? ooieoe?? – aeoeaaoe?? aei
oa?iaioo, iniiaia ?ieue yeiai iieyaa? a ?oeioaaii? o?a?eiiaiai caonoea a
e?iaioioe? oa aioo??oiueinoaeeiieo a?aeeeaaeaiue o?a?eio. Inoaii?i /anii
anoaiiaeaii, ui eiioi?iaoe?y iaoeaiiai ieaci?iiaaio ci?ith?oueny i?e
eiai aca?iiae?? c aeayeeie a?eeaie. Iai?eeeaae, iiiieeiiaeuei? aioe?ea
aei ie?aieo e?eiaeiaeo ae?eyiie ieaci?iiaaio ?oeiothoue ?nioth/? a
iieaeoe? aioo??oiueiiieaeoey?i? aca?iiae??, ui oaeiae i?eaiaeeoue aei
eiioi?iaoe?eieo ia?aaoaeia o iieaeoe? i?ioa?iaioo. Iaoeaia
(Glu-ieaci?iiaai) oa /anoeiai a?ae-?ie?ciaaia (Lys-ieaci?iiaai) oi?ie
i?ioa?iaioo neeueii ??ciyoueny caeaoi?noth aca?iiae?yoe c o?c?ieia?/iei
e?aaiaeii – o?a?eiii – oa /ooeea?noth aei ae?? i?e?iaeieo aeoeaaoi??a
ieaci?iiaaio. I?ney iao?eaaeiai ieaci?iiaiai a?ae?ie?co o?a?eio ??cei
ca?eueoo?oueny nii??aeiai?noue i?ioa?iaioo aei iueiai, ui i?eaiaeeoue
aei i?enei?aiiy aeoeaaoe?? ieaci?iiaaio oeaieiiei aeoeaaoi?ii.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie. Aeaia ?iaioa ?
i?iaeiaaeaiiyi ?ia?o ii aea/aiith iieaeoey?iiai iaoai?cio o?a?eiie?co,
ye? i?iaiaeeeenue o a?aeae?e? o?i?? oa a?io?i?? oa?iaio?a ?inoeoooo
a?io?i?? ?i.I.A.Iaeeaae?ia IAI Oe?a?ie i?ioyaii 1986 – 96 ??. o ?aieao
iaoeiai-aeine?aeii? oaie N17 ca i?iaeaiith “A?io?i?y oaa?ei ? ethaeeie”
(oeo?e 2.28.4.8 oa2.28.2.6). ?? aea?ae. ?a?no?aoe?? 01830064150,
01880076299, 01930012659.

Iaoa ? caaaeaiiy aeine?aeaeaiiy. Iaoith ?iaioe aoei aea/eoe aoaeoi?io
ae?th o?a?ei(iaai)o, /anoeiai a?ae?ie?ciaaiiai o?a?ei(iaai)o oa ?o
o?aaiaio?a ia ci?io aeanoeainoae Glu-ieaci?iiaaio.

A?aeiia?aeii aei iniiaii? iaoe a ?iaio? ae??ooaaeenue oae? caaaeaiiy:

Ii??aiyoe ca’ycoaaiiy Glu- oa Lys- oi?i ieaci?iiaaio c iaoeaiei oa
/anoeiai aeaa?aaeiaaiei o?a?eiii.

Iaea?aeaoe oa ioa?aeoa?ecoaaoe i?aia?aoe o?a?ei-iiiiia?a ??ciiai nooiaiy
aeaa?aaeaoe??.

Aeine?aeeoe aca?iiae?th Glu-ieaci?iiaaio c A-o?aaiaioii o?a?eiiaaio.

Ii??aiyoe aca?iiae?th aeaio oi?i ieaci?iiaaio c o?aaiaioaie
o?a?ei(iaai)o, ye? i?noyoue D-aeiiai.

Aea/eoe aieea /anoeiai? aeaa?aaeaoe?? o?a?eio ia oaeaee?noue a?ae?ie?co
o?a?eio ieaci?iii oa Glu- aai Lys-ieaci?iiaaiii i?e ?oi?e aeoeaaoe??
t-PA.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. Anoaiiaeaii, ui aca?iiae?y
Glu- oa Lys-ieaci?iiaaio c iaoeaiei o?a?eiii cae?enith?oueny
iaiaeiaeiaeie ae?eyieaie i?ioa?iaioo. Oae, ni?aoe?y Glu-ieaci?iiaaio ia
iaoeaiiio o?a?ei? caaacia/o?oueny iecueeiao?iiith ae?eyieith, a /anoeiai
aeaa?aaeiaaii? oi?ie i?ioa?iaioo – ae?eyieaie ye aeniei?, oae ? neaaoi?
nii??aeiaiino? aei e?ceio oa eiai aiaeia?a. Aia?oa iieacaii, ui i?e
aca?iiae?? Glu-ieaci?iiaaio c /anoeiai aeaa?aaeiaaiei o?a?eiii o
iieaeoe? i?ioa?iaioo a?aeaoaathoueny eiioi?iaoe?ei? ci?ie, a ?acoeueoao?
yeeo aei a?eie-a?eeiaeo aca?iiae?e caeo/athoueny aenieiao?ii? ca’ycoth/?
ae?eyiee iaoeaii? oi?ie i?ioa?iaioo. Naia ooai?aiiy O-o?aaiaio?a
ni?e/eiy? ia?ao?ae Glu-ieaci?iiaaio aei a?aee?eoi? eiioi?iaoe??,
i?eoaiaiii? Lys-ieaci?iiaaio.

I?e aeine?aeaeaii? aca?iiae?? iaoeaiiai ieaci?iiaaio c A-o?aaiaioii
o?a?eiiaaio niinoa??aaeiny ia?aoai?aiiy i?ioa?iaioo ia /anoeiai
aeaa?aaeiaaio oi?io. Aia?oa aoei anoaiiaeaii, ui ye eiiieaen
ieaci?iiaai-A-o?aaiaio, oae ? i?ioa?iaio i?ney aeenioe?aoe?? eiiieaeno
aeyaeythoue i?ioaie?oe/io aeoeai?noue. Oiaoi A-o?aaiaio o?a?ei(iaai)o
?iaeoeo? a iaoeaiiio ieaci?iiaai? oi?ioaaiiy aeoeaiiai oeaio?o, yea ?
?acoeueoaoii eiioi?iaoe?eieo ia?aaoaeia o iieaeoe? i?ioa?iaioo. Oaiiiai
eiioi?iaoe?eii? aeoeaaoe?? ieaci?iiaaio i?e aca?iiae?? c i?ci?ie
i?iaeoeoaie aeaa?aaeaoe?? o?a?ei(iaai)o iiaea aooe iaeiei c oeyo?a
?aaoeyoe?? o?a?eiie?oe/iiai i?ioeano.

Aia?oa iieacaii, ui ?iiia?e?ciaaiee DH-aeeia? o?a?eio ooai?th? eiiieaen
c Glu-ieaci?iiaaiii. ?ic?aoiaaii eiinoaioe aeenioe?aoe?? Glu- oa
Lys-ieaci?iiaaio c DH-aeeia?ii, ye? noaiiaeyoue 3,2(10-6 I oa 3,7(10-6 I
a?aeiia?aeii.

Aeine?aeaeaii aoaeoi?i? aeanoeaino? iaoeaiiai ? /anoeiai
a?ae?ie?ciaaiiai desAABB-o?a?eio uiaei ieaci?io. Iieacaii, ui ia
ii/aoeiaeo aoaiao a?ae?ie?co i?e a?aeuaieaii? (N-aeiiai?a ie?aieo
iieaeoe o?a?ei-iiiiia?a ca?eueoo?oueny nii??aeiai?noue ieaci?io aei
o?a?eio. Oeae oaeo aeicaiey? i?eionoeoe, ui c iiyaith O-iie?ia??a
i?ioaie?oe/ia ae?y ieaci?io uiaei o?a?eio oae naii, ye ? i?e aca?iiae??
c o?a?eiiaaiii, ?aaoeth?oueny aeiaeaoeiaeie e?cei-ca’ycoth/eie
ae?eyieaie.

Oai?aoe/ia oa i?aeoe/ia cia/aiiy ?iaioe. Ii/aoeia? aoaie a?ae?ie?co
iie?ia?iiai o?a?eio, eiee a?aeaoaa?oueny a?aeuaieaiiy (N-aeiiai?a
ie?aieo o?a?ei-iiiiia?ieo iaeeieoeue, aeeeeeathoue eiioi?iaoe?ei?
ia?aaoaeiae iaoeaiiai i?ioa?iaioo, aiane?aeie /iai a?i ia?aoiaeeoue aei
a?aee?eoi? eiioi?iaoe?? Lys-ieaci?iiaaio ? noa? aeinooii?oei aeey
aeoeaaoe??. Iaea?aeai? ?acoeueoaoe uiaei aoaeoi?ii? ae??
o?a?eiiaaio/o?a?eio oa ?o iio?aeieo ia aeanoeaino? Glu-ieaci?iiaaio
iiaeeaeththoue iao? oyaeaiiy i?i iieaeoey?iee iaoai?ci o?a?eiie?co.
I?iaaaeai? aeine?aeaeaiiy caeaa?eueoiai iinyoue oai?aoe/iee oa?aeoa?,
aea aiie iiaeooue noaoe iniiaith aeey ?ic?iaee iaoiae?a eiio?ieth ca
o?iiaie?oe/iith oa?ai??th oa noaiii nenoaie aaiinoaco i?e
na?oeaai-noaeeiieo caoai?thaaiiyo.

Iniaenoee aianie aeena?oaiaoa. Aenia?eiaioaeueio /anoeio ?iaioe, aeia??
oa ii?aoethaaiiy e?oa?aoo?e c?iaeaii aaoi?ii iniaenoi. Aiae?c oa
iaaiai?aiiy iaea?aeaieo ?acoeueoao?a i?iaaaeaii ni?eueii c iaoeiaei
ea??aieeii ae.a.i. Eoae?iiaei N.I. oa ea??aieeii a?oie e.a.i. A?eiaiei
O.A. Ae?oeiaai? i?aoe? i?aeaioiaeai? ca aaciina?aaeiuei? o/ano? aaoi?a.

Ai?iaaoe?y ?iaioe. Iniiai? ?acoeueoaoe oa ie?ai? iieiaeaiiy
aeena?oaoe?eii? ?iaioe aoee aeeeaaeai? ia eiieo?n? iieiaeeo o/aieo
?inoeoooo a?io?i?? ?i.I.A.Iaeeaae?ia IAI Oe?a?ie (Ee?a, 1987), ia VI
Oe?a?inueeiio a?io?i?/iiio c’?cae? (Ee?a, 1992), ia III neiiic?oi?
“Oeiey i?ioaieeoe/aneeo oa?iaioia” (Iineaa, 1993), ia XV i?aeia?iaeiiio
eiia?an? “Thrombosis and Haemostasis” (??onaeei, 1995), ia can?aeaiiyo
a?aeae?eo o?i?? oa a?io?i?? oa?iaio?a ?inoeoooo a?io?i??
?i.I.A.Iaeeaae?ia IAI Oe?a?ie (Ee?a, 1996), a?aeae?eo no?oeoo?e oa
ooieoe?? a?eea ?inoeoooo a?io?i?? ?i.I.A.Iaeeaae?ia IAI Oe?a?ie (Ee?a,
1999), ia iaoeiaiio nai?ia?? ?inoeoooo a?io?i?? ?i.I.A.Iaeeaae?ia IAI
Oe?a?ie (Ee?a, 1999).

Ioae?eaoe??. Ca iaoa??aeaie aeena?oaoe?? iioae?eiaaii 3 noaoo? oa oace 2
aeiiia?aeae.

No?oeoo?a oa ianya aeena?oaoe??. Aeena?oaoe?y aeeeaaeaia ia 135
noi??ieao iaoeiiieno oa neeaaea?oueny c ?icae?e?a “anooi”, “iaeyae
e?oa?aoo?e”, “iaoa??aee oa iaoiaee aeine?aeaeaiue”, “?acoeueoaoe
aeine?aeaeaiue oa ?o iaaiai?aiiy”, “Aeniiaee” oa “Nienie aeei?enoaieo
aeaea?ae”, ui iae?/o? 214 iaeeieoeue. ?iaioa ?ethno?iaaia 31 ?enoieii oa
5 oaaeeoeyie.

IAEssAe E?OA?AOO?E

Iaeyae e?oa?aoo?e neeaaea?oueny c i’yoe ?icae?e?a, a yeeo aena?oeai?
ieoaiiy no?oeoo?e oa eiioi?iaoe?eiiai noaio iieaeoee ieaci?i(iaai)o,
no?oeoo?e eiai ca’ycoth/eo ae?eyiie, no?oeoo?e iieaeoee o?a?eiiaaio,
i?e?iaee a?eie-a?eeiaeo aca?iiae?e i?ae Glu- oa Lys-ieaci?iiaaiii oa
o?a?ei(iaai)ii oa ?o i?ioaie?oe/ieie o?aaiaioaie.

Iaoa??aee oa iaoiaee aeine?aeaeaiUe

Glu-ieaci?iiaai ethaeeie aeae?eyee c ieacie aeiii?nueei? e?ia? oeyoii
ao?iii? o?iiaoia?ao?? ia e?cei-naoa?ic? 4A (Deutch, Mertz, 1970) c
ianooiiith aaeue-o?eueo?aoe??th ia naoaaeaen? G-150.

Lys-ieaci?iiaai io?eioaaee c o?aeoe?? aeiii?nueei? e?ia? III2,3 ca Eiiii
a oaeee naia niin?a, ui ? Glu-ieaci?iiaai (Deutch, Mertz, 1970), ia
aeiaeath/e ?ia?a?oi?a. Aaeue-o?eueo?aoe?th i?iaiaeeee i?e e?iiaoi?e
oaiia?aoo??.

Ieaci?i iaea?aeoaaee, aeoeaoth/e Lys-ieaci?iiaai no?aioie?iacith
(«Streptase» Oaaeoea??y) (Wiman, 1977).

I?ioaie?oe/io aeoeai?noue ieaci?io oa iioaioe?eio aeoeai?noue
ieaci?iiaaio aecia/aee ca ?o caeaoi?noth a?ae?ie?coaaoe eaca?i (ca
Aaia?noaiii) (Robbins, Summaria, 1979).

O?aaiaio ieaci?iiaaio E1-3 io?eioaaee oeyoii iaiaaeaiiai i?ioaie?co
Lys-ieaci?iiaaio naeiith iaie?aaoe/iith aeanoacith (Sottrup-Jensen et
al., 1978).

Aaaaeaiiy ?aae?iaeoeaii? i?oee 125? aei i?aia?aoo Glu-ieaci?iiaaio
i?iaiaeeee ca aeiiiiiaith oei?ai?io O (McConahey, Dixon, 1980). Ieoiia
?aae?iaeoeai?noue i?aia?aoo noaiiaeea 4,68 IAe/ia. I?/aiee a?eie ia
a?ae??ciyany a?ae aeo?aeiiai i? eaca?iie?oe/iith aeoeai?noth, i?
aeaeo?ioi?aoe/iith ?ooii?noth.

O?a?eiiaai aeae?eyee c ienaeaoii? ieacie e?ia? aeea o i?enooiino?
ni?aiai ?ia?a?oi?a o?eineio oeyoii aeniethaaiiy noeueoaoii iao??th
(Aa?aoeueea oa ?i., 1961) c aeiaeaoeiaei i/euaiiyi a?ae aeii?oie
ieaci?iiaaio (Mosseson, 1962). Ai?no o?a?eiiaaio, ui cn?aeaany i?ae
ae??th o?iia?io, noaiiaea 95-98%.

O?aaiaioe o?a?eiiaaio DH oa A io?eioaaee c ieaci?iiaiai a?ae?ie?caoo
o?a?eiiaaio, o?aaiaio Dla – iaineiie?cii DH-o?aaiaioa (Privalov,
Medved’, 1982; Medved’ et al., 1983, 1986, 1988).

*anoeiai aeaa?aaeiaaiee o?a?ei(iaai) iaea?aeoaaee ca aeiiiiiaith
iaiaaeaiiai ieaci?iie?co a 0,05 I iao??e oinoaoiiio aooa??, ?I 7,4
i?ioyaii 30 oa i?e 20°N. ?aaeoe?th coieiyee aeiaeaaaiiyi
ia?a-i?o?ioai?eaoai?aeeiaaicieii? oa 6-ai?iiaaenaiiai? eeneio, e?ioeaa?
eiioeaio?aoe?? yeeo noaiiaeee 10-4 oa 10-1 I a?aeiia?aeii. Nooi?iue
a?ae?ie?co o?a?eiiaaio (o a?aenioeao aei o?a?eiiaaio, yeee i?noeany a
i?ia?) aecia/aee ca e?euee?noth a?eea, yeee eeoeany a ?ic/ei? i?ney
ooai?aiiy caonoea oa eiai aeaeaeaiiy. Neeaae i?iaeoeo?a o?a?eiie?co
aecia/aee ca aeiiiiiaith aeaeo?ioi?aco a IAAA ca i?enooiino? AeN-iao??th
(Weber, 1969) ?ic/eiaieo a ioeoia?e eeneio? o?a?eiiaeo caonoe?a, ui
ooai?ai? c /anoeiai a?ae?ie?ciaaiiai o?a?eiiaaio.

Iaea?aeaiiy desAABB-o?a?eio i?iaiaeeee a 0,15 I oei?enoiio iao??? i?e
37(N ca i?enooiino? ia?a-oei?ia?eo??eaaicieii? eeneioe. Iaea?aeaiee a
oaeee niin?a o?a?ei-iiiiia? aoa a?eueiee a?ae ieaci?i(iaai)o, ine?eueee
?aaeoe?th cn?aeaiiy i?iaiaeeee ca iayaiino? 100 mM (-ai?iieai?iiiai?
eeneioe (Posdnjakova et al., 1979).

DH-aeeia? aeae?eyee c ieaci?iiaeo a?ae?ie?cao?a o?a?eio. Iaea?aeaiee
D-aeeia? aoa a?eueiee a?ae aeii?oie D- oa A-o?aaiaio?a (A?e?oea? oa ?i.,
1988).

Aeaeo?ioi?ac a iie?ae?eeai?aeiiio aae? (IAAA) i?iaiaeeee ca eeneeo
cia/aiue pH a nenoai? na/iaeia/ioeoiaa eeneioa aeey aecia/aiiy oi?ie
iaea?aeaiiai ieaci?iiaaio (Panyim, Chalkley, 1969) oa ca i?enooiino?
AeN-iao??th aeey aecia/aiiy /enoioe o?a?eiiaaio, o?a?eio, ?o o?aaiaio?a,
ieaci?iiaaio oa eiai o?aaiaio?a (Weber, Osborn, 1969; McDonagh et al.,
1972; Cummins, Perry, 1973).

Oaeaee?noue ?oeioaaiiy o?a?eiiaiai caonoea aecia/aee oo?a?aeeiao?e/iei
iaoiaeii (Bouvier et al., 1975).

Aea/aiiy aca?iiae?? Glu-ieaci?iiaaio c ?iiia?e?ciaaieie A-, DH-,
DL-o?aaiaioaie oa DH-aeeia?ii i?iaiaeeee iaoiaeii ao?iii? o?iiaoia?ao??
i?e 20(N.

Aeine?aeaeaiiy aca?iiae?? ieaci?iiaaio c o?a?eiii i?iaiaeeee a i?ioean?
ooai?aiiy o?a?eio, aeiaeath/e aei ?aaeoe?eiiai na?aaeiaeua
125I-Glu-ieaci?iiaai. Aeey a?aooaaiiy ianiaoeeo?/ii? ni?aoe?? aei
eiio?ieueieo i?ia aeiaeaaaee e?cei aei e?ioeaai? eiioeaio?aoe?? 0,05 I.
*a?ac 30 oa ?ieoaaoe?? i?e 37°N o?a?eiiaee caonoie, ui ooai?eany,
aeiiooaaee neeyieie iaee/eaie. I?ney oeueiai e?euee?noue a?eea a ?ic/ei?
aecia/aee niaeo?ioioiiao?e/iei iaoiaeii aai ca ?aae?iaeoeai?noth ia
e?/eeueieeo Beckman Gamma 5500 (NOA). E?euee?noue ieaci?iiaaio, ui
ca’ycaany c o?a?eiiaei caonoeii, ?ic?aoiaoaaee ca ??cieoeath i?ae
e?euee?noth a?eea aai ?aae?iaeoeai?noth, ui aiineeeny aei i?iae oa
eeoeeeny a ?ic/ei? i?ney aeaeaeaiiy o?a?eio oa ianiaoeeo?/ii ni?aiaaiiai
ieaci?iiaaio.

Ca’ycoaaiiy Glu- oa Lys-ieaci?iiaaio c /anoeiai a?ae?ie?ciaaiei o?a?eiii
oa aieea o?aaiaio?a ieaci?iiaaio ia aca?iiae?th ieaci?iiaaio c o?a?eiii
i?iaiaeeee ca oaeeo naieo oiia oa ni?aa?aeiioaiue aca?iiae?th/eo a?ee?a,
ye ? c iaoeaiei o?a?eiii, iaeiae o i?iae, ui i?noeee i?ioa?iaio, aiineee
o?a?ei-iiiiia?, io?eiaiee c /anoeiai a?ae?ie?ciaaiiai o?a?eiiaaio.

E?euee?nia oa?aeoa?enoeea ia?aoiaeo 125I-Glu-ieaci?iiaaio aei Lys-oi?ie
aoea iaea?aeaia ca aeiiiiiaith aeaeo?ioi?aoe/iiai aiae?co a?eeiaeo
o?aeoe?e, ye? aeththaaee (-ai?iieai?iiiaith eeneioith c
A-o?aaiaio-aaa?ice, aai ?ic/eiieo eiiieaen?a 125I-Glu-ieaci?iiaaio c
A-o?aaiaioii. I?ney oa?aoaaiiy oa aenooaiiy aae?a c ieo ae??caee a?eeia?
ciie, ?aae?iaeoeai?noue yeeo aei??thaaee ia e?/eeueieeo Beckman Gamma
5500 (NOA).

Aeoeai?noue eiiieaeno Glu-ieaci?iiaaio c ?ic/eiiei A-o?aaiaioii
aecia/aee ca iaoiaeii o?a?eiiaeo ieao?aie oa ca oaeaee?noth a?ae?ie?co
H-D-Val-L-Leu-L-Lys-ia?a-i?o?iai?e?aeo (S-2251) i?e 37°N.

?ACOEUeOAOE AeINE?AeAEAIUe OA ?O IAAIAI?AIIss

1. Aca?iiae?y Glu- oa Lys-ieaci?iiaaio c iaoeaiei o?a?eiii

?en. 1.2 Aieea (-AEE ia ca’ycoaaiiy Glu- (1) oa Lys- (2) ieaci?iiaaio c
desAABB-o?a?eiii, ooai?aiei c /ano-

eiai a?ae?ie?ciaaiiai o?a?eiiaaio, oa Glu- ieaci?ii-

aaio(3) c iaoeaiei o?a?eiii.

Ca’ycoaaiiy ieaci?iiaaio ia iie?ia?iiio o?a?ei? aea/aee a i?ioean?
iie?ia?ecaoe?? inoaiiueiai. I?e an?o aeine?aeaeaieo ni?aa?aeiioaiiyo
a?ee?a e?euee?noue ni?aiaaiiai Lys-ieaci?iiaaio aoea iaeaea a 7 ?ac?a
a?eueoa ca e?euee?noue Glu-ieaci?iiaaio. I?e ?ic?aooieo iaeneiaeueii?
e?eueeino? ieaci?iiaaio, ui iiaea ca’ycaoeny c 1 iieai o?a?ei-iiiiia?a
ca oiia aenia?eiaioo, anoaiiaeaii, ui oey aaee/eia aei??aith? aeecueei
0,5 oa 0,08 iiey aeey Lys- oa Glu-oi?ie a?aeiia?aeii (?en.1.1).

?en. 1.1 Caeaaei?noue e?eueeino? ca’yca-iiai Glu- (1) oa Lys- (2)
ieaci?iiaa-io a?ae e?eueeino? aianaiiai ieaci?iiaaio.

sse aeaeii c ?acoeueoao?a, iiaeaieo ia ?en.1.2, ca i?enooiino?
(-ai?iieai?iiiai? eeneioe a eiioeaio?aoe?yo, ye? iane/othoue
aenieiao?iio ae?eyieo, ciaioo?oueny e?euee?noue ni?aiaaiiai
Lys-ieaci?iiaaio, a e?euee?noue ni?aiaaiiai ca oeo naieo oiia iaoeaiiai
i?ioa?iaioo ia ci?ith?oueny. Ciaioaiiy ni?aoe?? Lys-oi?ie ia 50%
niinoa??aaeinue i?e eiioeaio?aoe?? ?ia?a?oi?a 8(10-5 I, ui
ocaiaeaeo?oueny c aeaieie (Suenson, Thorsen, 1987), io?eiaieie i?e
aeei?enoaii? o?aiaenaiiai? eeneioe. Oea aeicaiey? noaa?aeaeoaaoe, ui
aca?iiae?y aeaio oi?i i?ioa?iaioo c iaoeaiei o?a?eiii iiina?aaeeiaaia
ca’ycoth/eie ae?eyieaie ??cieo oei?a. Ni?aoe?y Lys-ieaci?iiaaio
a?aeaoaa?oueny ca ?aooiie aenieiao?iii? ae?eyiee, a Glu-ieaci?iiaaio –
ae?eyiee iecueei? nii??aeiaiino?.

Ca aeiiiiiaith iaoiaeo ao?iii? o?iiaoia?ao?? iieacaii, ui ca iayaiino?
o?aaiaioa E1-3 ieaci?iiaaio, yeee i?noeoue aenieiao?iio ae?eyieo, ia
ci?ith?oueny e?euee?noue Glu-ieaci?iiaaio, yeee ni?ao?oueny o i?ioean?
iie?ia?ecaoe?? ia iaoeaiiio o?a?ei?. Ui ae aei aieeao E1-3 ia
aca?iiae?th Lys-ieaci?iiaaio c iaoeaiei o?a?eiii, oi anoaiiaeaii
?ia?aoth/ee aoaeo o?aaiaioa, yeee i?noeoue aenieiao?iio ae?eyieo (Lucas,
1983). Iaeae?ia?aei?oa oea iia’ycaii c oei, ui Glu-ieaci?iiaai
ciaoiaeeoueny a cae?eo?e eiioi?iaoe??, yea ia aeicaiey? eiio ni?aoaaoeny
ia iaoeaiiio o?a?ei? ca aeiiiiiaith ae?eyiee, ?icoaoiaaii? a iaeano?
E1-3. Io?eiai? ?acoeueoaoe aeicaieythoue noaa?aeaeoaaoe, ui iecueea
nii??aeiai?noue iaoeaiiai ieaci?iiaaio aei o?a?eio, iiaeeeai,
iiina?aaeeiaaia aca?iiae??th iaei??? c oeo neaaeeo ca’ycoth/eo ae?eyiie,
yea ia aeyaey? nii??aeiaiino? aei a?a?i?io (Verevka et al., 1986).

Oiae, o?aoiaoth/e io?eiai? ?acoeueoaoe oa aeai? e?oa?aoo?e uiaei
ia/ooeeaino? ca’ycoth/i? ae?eyiee E4 aei a?a?i?io, iiaeia
noaa?aeaeoaaoe, ui aca?iiae?y Lys-ieaci?iiaaio c o?a?eiii
iiina?aaeeiaaia, ie??i ae?eyiee aeniei? nii??aeiaiino? (e?cei-ca’ycoth/a
ae?eyiea, ?icoaoiaaia a e?eiae? E1), ua e ?ioeie ae?eyieaie neaaoi?
nii??aeiaiino? aei aiaeia?a e?ceio, oiae? ye c aieo Glu-ieaci?iiaaio a
eiiieaeniooai?aii?, eiia??ii, aa?a o/anoue iecueeiao?iia ae?eyiea,
?icoaoiaaia a e?eiae? E4.

2. Aca?iiae?y Glu- oa Lys-ieaci?iiaaio c /anoeiai a?ae?ie?ciaaiei
o?a?eiii

Ca’ycoaaiiy ieaci?iiaaio c desAAAA-o?a?eiii aeine?aeaeoaaee a nenoai? c
iie?ia?iei o?a?eiii, yeee ooai?thaaee c /anoeiai aeaa?aaeiaaiiai
o?a?eiiaaio ??ciiai nooiaiy a?ae?ie?co. E?euee?noue ni?aiaaiiai
Lys-ieaci?iiaaio c?inoaea ia 5% i?e ca?eueoaii? nooiaiy
a?ae?ie?ciaaiino? aeo?aeiiai o?a?eiiaaio, c yeiai ooai?thaaee
desAABB-o?a?ei (?en.2.1). Cian?i ?ioith ca oiia aenia?eiaioo aoea
iiaaae?iea Glu-ieaci?iiaaio. Iaa?oue i?e iaeiaioiio nooiai? a?ae?ie?co
o?a?eiiaaio (ia aeua 0,5%) e?euee?noue ni?aiaaiiai a?eea ca?eueooaaeany
a e?eueea ?ac?a oa aeinyaaea iaeneiaeueiiai cia/aiiy, eiee nooi?iue
aeaa?aaeaoe?? o?a?eiiaaio noaiiaea 1-2%, ? ia ci?ithaaeanue i?e
iiaeaeueo?e aeaa?aaeaoe?? o?a?eiiaaio (?en.2.1).

?en. 2.1 Caeaaei?noue e?eueeino? ca’ycaii-

ai Glu- (1) oa Lys- (2) ieaci?iiaaio

a?ae nooiaiy a?ae?ie?ciaaiino?

o?a?eiiaaio.

?en. 2.2 Aieea e?eiaeo E1-3 ia ca’ycoaaiiy Glu-ieaci?iiaaio c iaoeaiei
(1) oa desAABB-o?a?eiii (2), ooai?aiei c /anoeiai a?ae?ie?ciaaiiai
o?a?eiiaaio

I?e aeine?aeaeaieo ni?aa?aeiioaiiyo aca?iiae?th/eo a?ee?a e?euee?noue
ca’ycaiiai c /anoeiai a?ae?ie?ciaaiei o?a?eiii iaoeaiiai i?ioa?iaioo
ca?eueooaa-eanue iaeaea a 10 ?ac?a ? nyaaea aaee/eie ni?aoe??
Lys-ieaci?iiaaio ia /anoeiai aeaa?aaeiaaiiio o?a?ei?. Caeaaei?noue
e?eueeino? ca’ycaiiai Glu-ieaci?iiaaio a?ae nooiaiy a?ae?ie?co
aeo?aeiiai o?a?eiiaaio ia? aeniiiaioe?eiee, a ia e?i?eiee oa?aeoa?. Ie
i?eionea?ii, ui naia ooai?aiiy O1-o?aaiaioa i?eaiaeeoue aei ci?i o
caeaoiino? Glu-ieaci?iiaaio aca?iiae?yoe c o?a?eiii.

O?aaiaio E1-3 neeueii i?eai?/o? ca’ycoaaiiy Glu-oi?ie c /anoeiai
aeaa?aaeiaaiei o?a?eiii (i?e 50-?aciaiio iiey?iiio iaaeeeoeo E1-3
ii??aiyii aei i?ioa?iaioo e?euee?noue ni?aiaaiiai ieaci?iiaaio
ciaioo?oueny ia 60%), a ni?aoe?y Glu-ieaci?iiaaio ia iaoeaiiio o?a?ei? a
i?enooiino? E1-3 eeoa?oueny iaci?iiith (?en.2.2).

Ca’ycoaaiiy ye Glu-, oae ? Lys-oi?ie ieaci?iiaaio c /anoeiai
a?ae?ie?ci-aaiei desAABB-o?a?eiii ca iayaiino? (-ai?iieai?iiiai? eeneioe
i?eai?/oaaeinue a eiioeaio?aoe?yo, ye? iane/othoue aenieiao?ii? ae?eyiee
(?en.1.2).

Iaea?aeai? ?acoeueoaoe aeicaieythoue noaa?aeaeoaaoe: i?e aca?iiae??
Glu-ieaci?iiaaio c /anoeiai aeaa?aaeiaaiei o?a?eiii o iieaeoe?
i?ioa?iaioo a?aeaoaathoueny oae? eiioi?iaoe?ei? ci?ie, ca yeeo aei
a?eie-a?eeiaeo aca?iiae?e caeo/athoueny aenieiao?ii? ca’ycoth/? ae?eyiee
iaoeaii? oi?ie i?ioa?iaioo. Naia ooai?aiiy O-o?aaiaio?a i?eaiaeeoue aei
ia?aoiaeo Glu-ieaci?iiaaio o a?aee?eoo eiioi?iaoe?th, i?eoaiaiio
Lys-oi?i?.

3. I?ioaie?oe/ia aeoeai?noue Glu-ieaci?iiaaio i?e eiai aca?iiae?? c

A-o?aaiaioii

Glu-ieaci?iiaai aeyaey? neaaeo nii??aeiai?noue aei DL-o?aaiaioa, yea
cia/ii ca?eueoo?oueny i?ney iiia?aaeiuei? aca?iiae?? iaoeaiiai
i?ioa?iaioo c ?iiia?e?ciaaiei A-o?aaiaioii. Aeey c’ynoaaiiy i?e/ei, ye?
aeeeeeathoue ci?ie aeanoeainoae i?ioa?iaioo, iaie aoa i?iaaaeaiee
aeaeo?ioi?aoe/iee aiae?c ieaci?iiaaio i?ney aeenioe?aoe?? eiiieaeno c
?iiia?e?ciaaiei A-o?aaiaioii. Iaaaaeai? ia ?en. 3.1 aeai? na?ae/aoue, ui
i?e aca?iiae?? 125?-Glu-ieaci?iiaaio c A-o?aaiaioii iinooiiai
c’yaey?oueny Lys-oi?ia. Oae, i?ioyaii ia?oeo i’yoe oaeeei
Glu-ieaci?iiaai caa??aa? naith ii/aoeiao, iaaeaa?aaeiaaio oi?io, a i?e
ca?eueoaii? /ano ?ieoaaoe?? eiiieaeno iaoeaiee i?ioa?iaio
ia?aoai?th?oueny o /anoeiai aeaa?aaeiaaio, iicaaaeaio NH2-e?ioeaaiai
iaioeaeo, oi?io – Lys-ieaci?iiaai. *a?ac 2 aiae eeoa aeecueei 30%
Glu-ieaci?iiaaio aeieaa?oueny c A-o?aaiaio-aaa?ice o ii/aoeiaiio
aeaeyae?, a ?aooa a?eea yaey? niaith Lys-ieaci?iiaai ? noi?o
iecueeiiieaeoey?ieo i?/aieo iaioeae?a. Caeaaeiee a?ae /ano ia?ao?ae
Glu-ieaci?iiaaio a Lys-oi?io niinoa??aaany ia o?eueee i?e aca?iiae??
i?ioa?iaioo c ?iiia?e?ciaaiei A-o?aaiaioii, a e i?e ?ieoaaoe?? i?ioyaii
e?eueeio aiaeei aea?iiey?ii? noi?o? oeeo a?ee?a a 0,05 I iao??e
oinoaoiiio aooa??, ?I 7,4 i?e 37(N. Ia aeaeo?ioi?aa?ai? i?ney
a?aeiiaeaiiy 2-ia?eaioiaoaiieii aeaeii ciaioaiiy ciie ieaci?iiaaio ?
iiyao ?aae?iaeoeaieo cii c ieae/ith iieaeoey?iith ianith, ye? yaeythoue
niaith aaaeeee ? eaaeee eaioethae ieaci?io aai i?iaeoeoe i?ioaie?co
ieaci?iiaaio (?en.3.2).

?en. 3.1 Caeaaei?noue ia?aoiaeo 125?-Glu -ieaci?iiaaio a Lys-oi?io a?ae
/ano

?nioaaiiy eiiieaeno c ?iiia?e?ciaaiei A-o?aaiaioii.

A – aeaeo?ioi?aoe/iee aiae?c o 11% IAAA a nenoai? na/iaeia/ioeoiaa
eeneioa, ?I 3,2: aeo?aeiiai Glu-ieaci?iiaaio (a) oa i?ioa?iaioo, yeee
aethth?oueny 0,1 I (-AEE /a?ac 5, 8, 10, 15, 30, 60 oa 120 oa (a, a, a,
ae, a, ae, c, a?aeiia?aeii), eiio?ieueiee c?acie — Lys-ieaci?iiaai (e);

A – ?iciiae?e ?aae?iaeoeaiino? aeaeo?ioi?aoe/ieo cii: 1-
Lys-ieaci?iiaai;

2 — Glu-ieaci?iiaai; 3 — iecueeiiieaeoey?i? iaioeaee.

?en. 3.2 Aeaeo?ioi?aa?aia a?aeiiaeaieo 2-ia?eaioiaoaiieii c?ace?a
125?-Glu-ieaci?iiaaio oa eiai eiiieaen?a c ?ic/eiiei A-o?aaiaioii:

1 – aeo?aeiee Glu-ieaci?iiaai;

2-5 – eiiieaene Glu-ieaci?iiaaio c A-o?aaiaioii, ye? ?ieoaoaaee i?e 37(N
i?ioyaii 1, 2, 3 oa 4 aiae.

?iciiae?e i?iaiaeeee o 10% DS-Na IAAA.

Iaea?aeai? ?acoeueoaoe aeicaieythoue i?eionoeoe, ui A-o?aaiaio i?e
ooa?aii? eiiieaeno c Glu-ieaci?iiaaiii aeeeeea? a iueiio eiioi?iaoe?ei?
ia?aaoaeiae, aiane?aeie yeeo c’yaey?oueny aeoeaiee oeaio?.

sse eiiieaen Glu-ieaci?iiaaio c ?ic/eiiei A-o?aaiaioii, oae ?
ieaci?iiaai, yeee aeththaaee c A-o?aaiaio-aaa?ice 0,1 I
(-ai?iieai?iiiaith eeneioith, aeyaey? o?a?eiie?oe/io aeoeai?noue (oaae.
3.1).

Eiia??i? aeii?oee aeoeaaoi??a ieaci?iiaaio a i?aia?aoao ieaci?iiaaio oa
A-o?aaiaioa ia?aa??yee iaoiaeii o?a?eiiaeo ieao?aie ? aecia/aiiyi
ieaci?iiai? aeoeaiino? ca a?ae?ie?cii o?iiiaaiiiai noano?aoo, ye?
aeicaieythoue cao?enoaaoe iaiiiiey?i? eiioeaio?aoe?? oa?iaioo a ?ic/ei?.
AEiaeiei c iacaaieo iaoiae?a o i?aia?aoao Glu-ieaci?iiaaio ? A-o?aaiaioa
aeoeaiino? aeyaeaii ia aoei. Ia iai?ia??oeo o?a?eiiaeo ieao?aeao i?
Glu-ieaci?iiaai, i? A-o?aaiaio ia aeaee cii e?ceno. Oiaoi a?eeia?
i?aia?aoe, ye? aeei?enoiaoaaeeny a ?iaio?, aoee a?eueieie a?ae aeii?oie
Oaaeeoey 3.1

O?a?eiie?oe/ia aeoeai?noue Glu-ieaci?iiaaio, ui aeieea? i?e eiai
aca?iiae?? c

A-o?aaiaioii o?a?eiiaaio, M±m

A?eie, yeee iaiineee ia o?a?eiia? ieao?aee, 10 iea

10 iea Ieiua cii e?ceno, ii2

Glu-ieaci?iiaai 0

A-o?aaiaio 0

Ieaci?i 113±4

Eiiieaen Glu-ieaci?iiaaio (10 iea) c A-o?aaiaioii (5 iea) 34±3

Ieaci?iiaai, ui aeieaa?oueny c A-o?aaiaio-aaa?ice* 25±5

*an aca?iiae?? Glu-ieaci?iiaaio c ?iiia?e?ciaaiei A-o?aaiaioii noaiiaea
2 aiae i?e e?iiaoi?e oaiia?aoo??. I?ney aethoe?? 0,1 I
(-ai?iieai?iiiaith eeneioith a?eie i?aeaeaaaee aaeue-o?eueo?aoe?? ia
naoaaeaen? G-50.

t-PA. Iaoiaeii aeaeo?ioi?aco a IAAA o nenoai? na/iaeia/ ioeoiaa eeneioa
i?ney ?ieoaaoe?? 125?-Glu-ieaci?iiaaio i?ioyaii 4 aiae ca iayaiino? oa
aac (-ai?iieai?iiiai? eeneioe i?e 37(N a 0,05 I iao??e oinoaoiiio
aooa??, ?I 7,4 aoei anoaiiaeaii, ui ieaci?iiaai caa??aa? naith iaoeaio,
iaaea-a?aaeiaaio oi?io.

Oi?ioaaiiy aeoeaiiai oeaio?o a eiiieaen? i?aeoaa?aeaeo?oueny oei, ui ca
iayaiino? ae??cii?ii?eooi?oinoaoo (AeOO) ia aoei a?aei?/aii ia?aoai?aiiy
Glu-ieaci?iiaaio ia Lys-oi?io. I?ae /an ?ieoaaoe?? aea?iiey?ii? noi?o?
a?ee?a ca iayaiino? ?ia?a?oi?a (eiioeaio?aoe?y yeiai noaiiaeoue 10-2 I)
i?ioyaii 2 aiae i?e 37(N i?ioa?iaio caa??aa? iaoeaio, iaaeaa?aaeiaaio
oi?io, iiia?aaeiy ae ia?iaea ?ia?a?oi?ii ?iaeea?aeoaeueieo a?ee?a c
ianooiiei eiai a?aeie?aieaiiyi ia aieeaaea ia caeaoi?noue eiiieaeno
i?iyaeyoe i?ioaie?oe/io aeoeai?noue (?en.3.3).

Ooai?aiiy eiiieaeno Glu-ieaci?iiaaio c A-o?aaiaioii caaacia/o?oueny
eiiieaiaioa?ieie oeaio?aie eiaeii? c iieaeoe, oiaoi aeoeai?noue
eiiieaeno caeaaeeoue a?ae iane/aiino? ae?eyiie ca’ycoaaiiy ye
ieaci?iiaaiii, oae ? A-o?aaiaioii. Iaeneiaeueia aeoeai?noue eiiieaeno
a?aeiia?aeaea 5-10-?aciaiio iaaeeeoeo iaeiiai c a?ee?a ii??aiyii aei
?ioiai. A?aeiii, ui Glu-ieaci?iiaai aca?iiae?? c A- o?aaiaioii aeaiia
oeaio?aie ??cii? nii??aeiaiino? c eiinoaioaie aeenioe?aoe??, ye?

?en. 3.3 ?ia?aoaaiiy i?ioaie?oe/ii? aeoeaiino? eiiieaeno
Glu-ieaci?iiaaio c ?ic/eiiei A-o?aaiaioii AeOO: 1 — eiio?ieueiee c?acie
Lys-ieaci?iiaaio;

2 — eiio?ieueiee c?acie Glu-ieaci?iiaaio;

3 — noi?o Glu-ieaci?iiaaio c A-o?aaiaioii i?ney ?ieoaaoe?? i?ioyaii 2
aiae i?e 37(N ca iayaiino? 1(10-2 I AeOO; 4 — oa ae naia, aea ca
a?aenooiino? AeOO.

aei??aiththoue 1,8(10-6 oa 7,5(10-6 I (A?eiaiei oa ?i., 1989).
(-ai?iieai?iiiaa eeneioa a eiioeaio?aoe?yo, ye? iane/othoue
e?cei-ca’ycoth/? ae?eyiee ieaci?iiaaio, i?eai?/o? i?ioaie?oe/io
aeoeai?noue eiiieaeno iaoeaiiai i?ioa?iaioo c ?ic/eiiei A-o?aaiaioii. C
e?oa?aoo?e a?aeiii, ui eiioi?iaoe?ei? ci?ie a iaoeaiiio i?ioa?iaio?
a?aeaoaathoueny ye i?e iane/aii? eiai neaaeeo e?cei-ca’ycoth/eo
ae?eyiie, oae ? i?e a?aeuaieaii? NH2-e?ioeaaiai iaioeaeo (Ponting,
1998). Ie aaaaea?ii, ui eiioi?iaoe?y Glu-ieaci?iiaaio iiaea ci?ithaaoeny
naia i?e iane/aii? iaei??? c neaaeeo e?cei-ca’ycoth/eo ae?eyiie
A-o?aaiaioii o?a?eiiaaio.

?en. 3.4 Caeaaei?noue ai?aeie?oe/ii? aeoeaiino? eiiieaeno
Glu-ieaci?iiaaio c A-o?aaiaioii a?ae /ano eiai ?nioaaiiy. Ia in? aanoeen
– /an ia?aae?ieoaaoe?? eiiieaeno.

Aeey ?ic?aooieo oaeaeeino? aeieeiaiiy ieaci?io i?e ooai?aii? eiiieaeno
Glu-ieaci?iiaaio c ?ic/eiiei A-o?aaiaioii aeei?enoiaoaaee o?iiiaaiiee
niaoeeo?/iee aeey ieaci?io noano?ao – S2251 (Wiman, 1980). Aea?iiey?io
noi?o Glu-ieaci?iiaaio oa A-o?aaiaioa ?ieoaoaaee i?e 37(N, aeiaeaaaee
aei ?ic/eio noano?aoo, aecia/aee e?euee?noue p-i?o?iai?e?io (p-NA), yeee
aea?eueiy?oueny. C io?eiaieo e?iaoe/ieo e?eaeo ?ic?aoiaoaaee e?euee?noue
p-NA, ui ooai?eany, a eiaeiiio aeiaaeeo a ii/aoeiaee ia??iae ?aaeoe??
(/a?ac 2 oa i?ney ?? ii/aoeo) (?en.3.4). Anoa-iiaeaii, ui oaeaee?noue
iiyae a nenoai? ieaci?io caeaaeeoue a?ae /ano ?nioaaiiy eiiieaeno. sse
aeaeii, aeoeai?noue noa? iaeneiaeueiith /a?ac 30 oa i?ney ooai?aiiy
eiiieaeno, a iio?i ii/eia? cieaeoaaoeny. Ie i?eionea?ii, ui aiaeii/an c
aeoeaaoe??th eaea i?ioean ?iaeoeaaoe??, yeee coiiaeaiee aaoie?cii
ieaci?io, yeee ooai?eany.

Oaeei /eiii, iiaeia noaa?aeaeoaaoe, ui A-o?aaiaio o?a?eiiaaio,
ci?ithth/e eiioi?iaoe?th Glu-ieaci?iiaaio, ?iaeoeo? a iueiio oi?ioaaiiy
aeoeaiiai oeaio?o. Ie i?iiiio?ii aeaa, ia ia?oee iiaeyae, i?ioeeaaei?
iiyniaiiy o?c?ieia?/iiai ci?noo oeueiai yaeua. Ia?oa. Eiioi?iaoe?eia
oi?ioaaiiy aeoeaiiai oeaio?o i?eaiaeeoue aei a?eueo oaeaeeiai aeaeaeaiiy
ieaci?iiaaio c i?noey eieeoiueiai caonoea ca ?aooiie ?iaeoeaaoe?? eiai
(2-aioeieaci?iii. Ae?oaa. Aeieeiaiiy i?e ni?aoe?? Glu-ieaci?iiaaio ia
A-o?aaiaio? aeoeaieo oeaio??a o i?ioa?iaio? i?eaiaeeoue aei ??ceiai, aea
iao?eaaeiai ca?eueoaiiy eieaeueii? eiioeaio?aoe?? aeoeaiiai oa?iaioo, ui
iiaea aooe aaaeeeaei aeey ?ic/eiaiiy aioo??oiueinoaeeiieo o?a?eiiaeo
caonoe?a. Iaeaeaa i?eiouaiiy na?ae/aoue, ui iiae?aia aeoeaaoe?y
i?ioa?iaioo i?e aca?iiae?? c i?ci?ie i?iaeoeoaie aeaa?aaeaoe??
o?a?eiiaaio iiaea aooe iaeiei c oeyo?a ?aaoeyoe?? o?a?eiie?oe/iiai
i?ioeano.

4. Aeaye? iniaeeaino? aca?iiae?? aeaio oi?i ieaci?iiaaio c o?aaiaioaie D
o?a?ei(iaai)o

Ia?ao?ae ?ic/eiiiai o?a?eiiaaio o oi?io iie?ia?iiai o?a?eio i?ae ae??th
o?iia?io oa?aeoa?eco?oueny cia/ieie eiioi?iaoe?eieie ci?iaie
neeaaeiii?aai?ciaaii? aaaaoiaeiiaiii? iieaeoee. I?e ooai?aii?
i?ioio?a?ee (N-aeiiaie iaei??? iieaeoee aca?iiae?thoue c oaeeie
non?aeiuei?. Anoaiiaeaii, ui a?aeaoaa?oueny aca?iiae?y ia eeoa i?ae E1D1
oeaio?aie, a e o N-e?ioeaaeo ae?eyieao (-eaioetha?a non?aei?o iieaeoe,
ye? iio?i i?ioeaathoueny oaeoi?ii O???a. ?ai?oa aoei anoaiiaeaii, ye?
o?aaiaioe o?a?eiiaaio i?noyoue ieaci?iiaai-ca’ycoth/? oeaio?e (Eaaeai,
1987), i?ioa ieoaiiy, ye? ae naia c ieo aaaeeea? aeey ni?aoe??
ieaci?iiaaio ia i?ioeoiio iie?ia?iiio o?a?ei?, eeoaeiny ia c’yniaaiei.

I?e aea/aii? aca?iiae?? Glu- oa Lys-oi?i ieaci?iiaaio c ??cieie
D-o?aaiaioaie iaoiaeii ao?iii? o?iiaoia?ao?? aoei iieacaii, ui c
DH-o?aaiaioa Lys-ieaci?iiaai aethth?oueny eeoa 0,1 I a?a?i?iii, oea
ca?aa?oueny c aeaieie uiaei ni?aoe?? eaaeiai eaioethaa ia oeueiio
o?aaiaio? (Tran-Thang, 1986). Oae? ?acoeueoaoe aeicaieeee i?eionoeoe, ui
D-aeiiaie o?a?eiiaaio i?noyoue oeaio?e, eiiiea-iaioa?i?
a?a?i?e-ca’ycoth/ei ae?eyieai Lys-ieaci?iiaaio. Aiaeii/an aoei
anoaiiaeaii, ui i?e iiaeaeueoiio a?ae?ie?c? DH-o?aaiaioa ia eiai
iecueeiiieaeoey?ieo oi?iao aeniiiothoueny ae?eyiee, eiiieaiaioa?i?
neeueiei e?cei-ca’ycoth/ei ae?eyieai ieaci?iiaaio.

Iaoiaeii ao?iii? o?iiaoia?ao?? iieacaii, ui Glu- oa Lys-oi?ie
ieaci?iiaaio aca?iiae?thoue c DH-aeeia?ii eeoa ca ?aooiie
e?cei-ca’ycoth/eo ae?eyiie, ine?eueee 0,1 I (-ai?iieai?iiiaa eeneioa
iiai?noth ?oeioaaea ?o aca?iiae?th. Anoaiiaeaii, ui eiinoaioa
aeenioe?aoe?? eiiieaeno Glu-ieaci?iiaai*DH-aeeia? aei??aith? 3,2(10-6 I,
a aeey eiiieaeno Lys-ieaci?iiaai*DH-aeeia? – 3,7(10-6 I. Oe? eiinoaioe
aeoaea aeecuee? iaeia aei iaeii? ia a?aei?io a?ae eiinoaio aeenioe?aoe??
Glu- oa Lys-ieaci?iiaaio c DL-o?aaiaioii (oaae. 4.1).

I?ney iao?eaaeiai ieaci?iiaiai a?ae?ie?co o?a?eio ??cei ca?eueoo?oueny
nii??aeiai?noue i?ioa?iaioo aei iueiai, ui iiynith?oueny iiyaith ia
iieaeoe? o?a?eio iiaeo ieaci?iiaai-ca’ycoth/eo oeaio??a. I?e ooai?aii?
/anoeiai aeaa?aaeiaaiiai o?a?eio aeniiiothoueny ieaci?iiaai-ca’ycoth/?
oeaio?e, ?icoaoiaai? a D-aeiiai?.

Oaaeeoey 4.1

E?euee?nia oa?aeoa?enoeea aca?iiae?? ieaci?iiaaio c o?a?eiiaaiii,

DL-o?aaiaioii oa DH-aeeia?ii

Ieaci?iiaai Ed, ieI

o?a?eiiaai DL-o?aaiaio DH-aeeia?

Lys-oi?ia 5,6 0,44 * 3,7

Glu-oi?ia ia aca?iiae?? 20,0 3,2

* Eoae?iia N.I., Aiae??aiia N.?., Eaaeai O.?., 1988

5. Aeine?aeaeaiiy oaeaeeino? a?ae?ie?co iaoeaiiai oa /anoeiai
a?ae?ie?ciaaiiai

o?a?eio ieaci?iii. Aoaeoi?i? aeanoeaino? /anoeiai a?ae?ie?ciaaiiai
desAABB-o?a?eio uiaei oaeaeeino? a?ae?ie?co o?a?eio Glu- oa
Lys-ieaci?iiaaiii, aeoeaiaaieie t-PA.

Iie?ia?iee o?a?ei aenooia?, c iaeiiai aieo, ye noeioethth/ee oaeoi?
aeoeaaoe?? ieaci?iiaaio oeaieiiei aeoeaaoi?ii, a c ae?oaiai aieo, naia
a?i ? ? i?e?iaeiei noano?aoii aeey ooai?aiiai ieaci?io. Aoaeoi?i?
aeanoeaino? iie?ia?iiai o?a?eio coiiaeai? iayai?noth a iueiio
ca’ycoth/eo ae?eyiie ye aeey ieaci?iiaaio, oae ? aeey oeaieiiiai
aeoeaaoi?a. A?aeiii, ui naia oi?ioaaiiy iio??eiiai eiiieaeno: oeaieiiee
aeoeaaoi? ieaci?iiaaio–o?a?ei–ieaci?iiaai ? iaiao?aeiith oiiaith
ooai?aiiy ieaci?io, oiaoi o?a?ei i?ae ? i?noeii i?ae i?ioa?iaioii oa
eiai aeoeaaoi?ii. Aiaeii/an, ni?aoe?y ia o?a?ei? oeaieiiiai aeoeaaoi?a
oa ieaci?io caoeua? ?o a?ae ae?? ?ia?a?oi??a.

Iaoith noaei ii??aiyoe oaeaeeino? a?ae?ie?co iaoeaiiai oa /anoeiai
aeaa?aaeiaaiiai iie?ia?iiai o?a?eio ye ieaci?iii, oae ? Glu- oa
Lys-ieaci?iiaaiii i?e ?o aeoeaaoe?? t-PA.

Aeei?enoaiiy iaoiaeo aecia/aiiy oa?i?io iai?ae?ceno o?a?eiiaiai caonoea
aeicaiey? aeine?aeaeoaaoe oaeaee?noue ?ic/eiaiiy o?a?eio ieaci?iii ii
anueiio ia’?io. Iniiaiei iieacieeii aoaeoeaiino? i?ioeano o?a?eiie?co
aoea ci?ia na?oei?icn?thaaiiy o?a?eiiaiai caonoea i?e 350 ii.
Oaeaee?noue a?ae?ie?co o?a?eio aecia/aee ca aaee/eiith t1/2, yea
oa?aeoa?ecoaaea /an, iaiao?aeiee aeey ciaiaiiy iaeneiaeueiiai
na?oei?icn?thaaiiy ia 50%, aecia/aiiy ae /ano, iaiao?aeiiai aeey iiaiiai
?ic/eiaiiy caonoea, aeicaieeei ?ic?aooaaoe oaeaee?noue aeaa?aaeaoe??
o?a?eio o iea a?eea ca iaeio oaeeeio.

Iaie anoaiiaeaii: yeui i?aia?ao o?a?ei-iiiiia?a i?noeoue a?eueoa 5%
O-o?aaiaio?a, ci?ia /ano iai?ae?ceno ia ? aeoaea ??ceith. Aiaeii/an
oaeaee?noue ieaci?iie?co cia/ii c?inoa? ?c ca?eueoaiiyi nooiaiy
a?ae?ie?co aeo?aeiiai o?a?eio. Ca?eueoaiiy oaeaeeino? ia 30 %
niinoa??aaeiny i?e a?aeuaieaii? 1,5-3% iieaeoey?ii? iane aeo?aeiiai
o?a?eiiaaio. Iieaeoey?ia iana (C-aeiiai?a noaiiaeoue /aoaa?oo /anoeio
iieaeoey?ii? iane o?a?eiiaaio, oaeei /eiii, a?aeuaieaiiy iaa?oue
iaaaeeei? e?eueeino? C-e?ioeaaeo iaioeae?a a?ae A(-eaioetha?a ?
aeinoaoiueith oiiaith i?enei?aiiy i?ioeano o?a?eiie?co.

Aeine?aeaeaiiy caeaaeiino? oaeaeeino? ieaci?iie?co a?ae eiioeaio?aoe??
o?a?ei-iiiiia?a ca noaei? eiioeaio?aoe?? oa?iaioo aeicaieeei ?ic?aooaaoe
eiinoaioe I?oaae?na: 7(10-6 M oa 3,3(10-6 I aeey ieaci?io i?e a?ae?ie?c?
iaoeaiiai oa /anoeiai aeaa?aaeiaaiiai o?a?eio a?aeiia?aeii. Oe? aeai?
na?ae/aoue i?i ca?eueoaiiy nii??aeiaiino? oa?iaioo aei noano?aoo ia
ii/aoeiaeo aoaiao a?ae?ie?co. Ca?eueoaiiy nii??aeiaiino? ieaci?io aei
/anoeiai a?ae?ie?ciaaiiai o?a?eio aeicaiey? i?eionoeoe, ui X-iie?ia?e
a?ae?a?athoue ?aaoeyoi?io ?ieue a i?ioean? o?a?eiie?co.

Anoaiiaeaii, ui oaeaee?noue ieaci?iie?co iie?ia?iiai o?a?eio ye Glu-,
oae ? Lys-ieaci?iiaaiii, aeoeaiaaieie t-PA, caeaaeeoue a?ae iaoeaiino?
aeo?aeiiai o?a?eio. Oaeaee?noue a?ae?ie?co iaoeaiiai o?a?eio
ieaci?iii, ui ooai?th?oueny

?en. 5.1 Ci?ia oaeaeeino? a?ae?ie?co o?a?eiiaiai caonoea, ooai?aiiai c
iaoeaiiai oa /anoeiai a?ae?ie?ciaaiiai o?a?eiiaaio (aecia/aee ye oaiaain
eooa iaoeeo aeioe/ii? /a?ac 2,5 oa aeey iaoeaiiai o?a?eio oa 50 n aeey
/anoeiai a?ae?ie?ciaaiiai o?a?eio).

i?e aeoeaaoe?? Lys-oi?ie t-PA, iaeaea a aeaa ?ace a?eueoa ca oaeaee?noue
a?ae?ie?co i?e aeoeaaoe?? Glu-ieaci?iiaaio. Aiaeii/an i?e a?ae?ie?c?
o?a?eio, noi?iiaaiiai c /anoeiai a?ae?ie?ciaaiiai o?a?eiiaaio,
oaeaeeino? noathoue iaeiaeiaeie (?en. 5.1). Oeae oaeo oe?eeii
ocaiaeaeo?oueny ?c c?iaeaiei aeniiaeii, ui aei aca?iiae?? c /anoeiai
aeaa?aaeiaaiei o?a?eiii caeo/athoueny o? ae ae?eyiee Glu-ieaci?iiaaio,
ui a?aeiia?aeathoue ca ni?aoe?th Lys-oi?ie i?ioa?iaioo ia iaoeaiiio
o?a?ei?.

Aeniiaee

Anoaiiaeaii, ui ni?aoe?y Glu-ieaci?iiaaio ia iaoeaiiio o?a?ei?
caaacia/o?oueny iecueeiao?iiith ae?eyieith, a aca?iiae?y
Lys-ieaci?iiaaio c iaoeaiei o?a?eiii iiina?aaeeiaaia ye aeniei-, oae ?
iecueeiao?iiith aei aiaeia?a e?ceio ae?eyieith.

Anoaiiaeaii, ui /anoeiai aeaa?aaeiaaiee (aei noaae?? O-o?aaiaio?a)
o?a?ei aeeeeea? a iaoeaiiio ieaci?iiaai? cia/i? eiioi?iaoe?ei? ci?ie, a
?acoeueoao? yeeo aca?iiae?y Glu-ieaci?iiaaio c oaeei o?a?eiii
a?aeaoaa?oueny ca ?aooiie aenieiao?iieo ca’ycoth/eo ae?eyiie, a
e?euee?noue ca’ycaiiai Glu-ieaci?iiaaio ca?eueoo?oueny a 10 ?ac?a.

Anoaiiaeaii, ui A-o?aaiaio o?a?eiiaaio i?e aca?iiae?? c
Glu-ieaci?iiaaiii ?iaeoeo? a inoaiiueiio eiioi?iaoe?eia oi?ioaaiiy
aeoeaiiai oeaio?o ? iiyao ieaci?io. Oaea aeoeaaoe?y i?ioa?iaioo i?e
aca?iiae?? c i?ci?ie i?iaeoeoaie aeaa?aaeaoe?? o?a?ei(iaai)o iiaea aooe
iaeiei c oeyo?a ?aaoeyoe?? o?a?eiie?oe/iiai i?ioeano.

Aeine?aeaeaii aca?iiae?th Glu- oa Lys-ieaci?iiaaio c D-o?aaiaioii
o?a?eiiaaio oa DH-aeeia?ii o?a?eio. Aia?oa iieacaii caeaoi?noue
DH-aeeia?a aca?iiae?yoe c Glu-oi?iith ieaci?iiaaio. ?ic?aoiaaii
eiinoaioe aeenioe?aoe?? Glu- oa Lys-ieaci?iiaaio c ?iiia?e?ciaaiei
DH-aeeia?ii, ye? noaiiaeyoue 3,2(10-6 I oa 3,7(10-6 I a?aeiia?aeii.
Anoaiiaeaii, ui ooai?aiiy D-aeeia?a noi?iaiaeaeo?oueny ci?iith
ieaci?iiaai-ca’ycoth/eo aeanoeainoae D-o?aaiaio?a, ui aoiaeyoue aei eiai
neeaaeo.

Aeine?aeaeaii aoaeoi?i? aeanoeaino? iaoeaiiai ? /anoeiai
a?ae?ie?ciaaiiai desAABB-o?a?eio uiaei ieaci?io. Iieacaii, ui ia
ii/aoeiaeo aoaiao a?ae?ie?co i?e a?aeuaieaii? (N-aeiiai?a ie?aieo
iieaeoe o?a?ei-iiiiia?a ca?eueoo?oueny nii??aeiai?noue ieaci?io aei
o?a?eio. Oeae oaeo aeicaiey? i?eionoeoe, ui c iiyaith O-iie?ia??a
i?ioaie?oe/ia ae?y ieaci?io uiaei o?a?eio oae naii, ye ? i?e aca?iiae??
c o?a?eiiaaiii, ?aaoeth?oueny aeiaeaoeiaeie e?cei-ca’ycoth/eie
ae?eyieaie.

ia?ae?e ?ia?o, ui iioae?eiaai? ca oaiith aeena?oaoe??

Neiii?ianueea I.A., A?eiaiei O.A., O?aoy/aiei A.A., Eoae?iia N.I.
I?ioaie?oe/ia aeoeai?noue Aeo-ieaci?iiaaio i?e eiai aca?iiae?? c
A-o?aaiaioii o?a?eiiaaio //Aeii. AI O?N?, na??y “A”. – 1988. – N10. –
N.72-75.

Neiii?ianeay A.A., A?eiaiei O.A., Eoaeeiia N.A., Cieioa?aaa Y.I.
Enneaaeiaaiea i?ioaieeoe/aneie aeoeaiinoe eiiieaena Glu-ieacieiiaaia n
A-o?aaiaioii oea?eiiaaia// Aeioeiey. – 1991. – 56, N 3. – N.458-466.

A?eiaiei O.A., Neiii?ianeay A.A., Eoaeeiia N.A., Cieioa?aaa Y.I.
Iniaaiiinoe acaeiiaeaenoaey Glu- e Lys-oi?i ieacieiiaaia n iaoeaiui e
/anoe/ii aeae?ieeciaaiiui oea?eiii //Aeioeiey. – 1992. – 57, N 5. –
N.728-729.

A?eiaiei O.A., Neiii?ianeay A.A., Cieioa?aaa Y.I., Eoaeeiia N.A.
Eco/aiea eiiieaeniia?aciaaiey ?acee/iuo oi?i ieacieiiaaia n oea?eiii //
III neiiiceoi “Oeiey i?ioaieeoe/aneeo oa?iaioia”, Iineaa, 1993. – N.80.

Skomorovskaya E.V., Grinenko T.V., Platonova T.N Interaction between
Glu-plasminogen and Lys-plasminogen with DH-dimer //XV International
Congress on Thrombosis and Haemostasis, Jerusalem, 1995. – P. 1136. – A
906.

Aiioaoe?y

Neiii?ianueea-I?ieaie?o I. A. Aoaeoi?ia ae?y o?a?eiiaaio/o?a?eio oa ?o
o?aaiaio?a ia aeanoeaino? Glu-ieaci?iiaaio. – ?oeiien.

Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe
ca niaoe?aeuei?noth 03.00.04 – a?io?i?y. – ?inoeooo a?io?i??
?i.I.A.Iaeeaae?ia IAI Oe?a?ie. Ee?a, 1999.

Aeena?oaoe?th i?enay/aii aea/aiith ci?i aeanoeainoae Glu-ieaci?iiaaio
i?e eiai aca?iiae?? c o?a?eiiaaiii/o?a?eiii oa ?o i?ioaie?oe/ieie
o?aaiaioaie. Iieacaii, ui ci?ia ni?aoe?eieo aeanoeainoae Glu- ? Lys-oi?i
i?ioa?iaioo iia’ycaia ia eeoa c aeniiioaaiiyi iiaeo
ieaci?iiaai-ca’ycoth/eo oeaio??a ia iieaeoe? o?a?eiiaaio/o?a?eio, a e c
eiioi?iaoe?eiei noaiii iieaeoee iaoeaiiai i?ioa?iaioo. *anoeiai
a?ae?ie?ciaaiee (aei noaae?? O-o?aaiaio?a) o?a?ei ?iaeoeo? a iaoeaiiio
ieaci?iiaai? cia/i? eiioi?iaoe?ei? ci?ie, a ?acoeueoao? yeeo
Glu-ieaci?iiaai ia?aoiaeeoue a Lys-ieaci?iiaai iiae?aiee noai.
Aca?iiae?y c oaeei o?a?eiii a?aeaoaa?oueny ca aenieiao?iieie
ca’ycoth/eie ae?eyieaie iaoeaiiai i?ioa?iaioo. Aia?oa iieacaii, ui
A-o?aaiaio o?a?eiiaaio ?iaeoeo? eiioi?iaoe?eia oi?ioaaiiy aeoeaiiai
oeaio?o a iieaeoe? Glu-ieaci?iiaaio. Eiioi?iaoe?eia aeoeaaoe?y
i?ioa?iaioo i?e aca?iiae?? c i?ci?ie i?iaeoeoaie aeaa?aaeaoe??
o?a?eiiaaio/o?a?eio iiaea aooe iaeiei c oeyo?a ?aaoeyoe??
o?a?eiie?oe/iiai i?ioeano. Aia?oa iieacaii, ui DH-aeeia? o?a?eio
ooai?th? eiiieaen c Glu-ieaci?iiaaiii. Iieacaii, ui ia ii/aoeiaeo aoaiao
a?ae?ie?co i?e a?aeuaieaii? (N-aeiiai?a ie?aieo iieaeoe o?a?ei-iiiiia?a
ca?eueoo?oueny nii??aeiai?noue ieaci?io aei o?a?eio. C iiyaith
O-iie?ia??a i?ioaie?oe/ia ae?y ieaci?io uiaei o?a?eio oae naii, ye ? i?e
aca?iiae?? c o?a?eiiaaiii, ?aaoeth?oueny aeiaeaoeiaeie
e?cei-ca’ycoth/eie ae?eyieaie.

Eeth/ia? neiaa: o?a?ei, X- oa E-o?aaiaio o?a?eiiaaio, DH-aeeia? o?a?eio,
Glu- oa Lys-ieaci?iiaai, i?ioaie?oe/ia aeoeai?noue, aeoeaiee oeaio?.

Aiiioaoeey

Neiii?ianeay-I?ieaieeo A. A. Yooaeoi?iia aeaenoaea oea?eiiaaia/oea?eia e
eo o?aaiaioia ia naienoaa Glu-ieacieiiaaia. – ?oeiienue.

Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 03.00.04 – aeioeiey. – Einoeooo aeioeiee
ei.A.A.Iaeeaaeeia IAI Oe?aeiu. Eeaa, 1999.

Aeenna?oaoeey iinayuaia eco/aieth eciaiaiee naienoa Glu-ieacieiiaaia i?e
aai acaeiiaeaenoaee n oea?eiiaaiii/oea?eiii e eo i?ioaieeoe/aneeie
o?aaiaioaie. Iieacaii, /oi eciaiaiea ni?aoeeiiiuo naienoa Glu- e
Lys-oi?i i?ioa?iaioa naycaii ia oieueei n yeniiie?iaaieai iiauo
ieacieiiaai-naycuaathueo oeaio?ia ia iieaeoea oea?ei(iaai)a, a e n
eiioi?iaoeeiiiui ninoiyieai iieaeoeu iaoeaiiai i?ioa?iaioa. *anoe/ii
aeae?ieeciaaiiue (aei noaaeee O-o?aaiaioia) oea?ei eiaeooee?oao a
iaoeaiii ieacieiiaaia cia/eoaeueiua eiioi?iaoeeiiiua eciaiaiey, a
?acoeueoaoa eioi?uo Glu-ieacieiiaai ia?aoiaeeo a Lys-ieacieiiaai
iiaeiaiia ninoiyiea. Acaeiiaeaenoaea n oaeei oea?eiii i?ienoiaeeo ii
aunieiaooeiiui naycuaathuei o/anoeai iaoeaiiai i?ioa?iaioa. Aia?aua
iieacii, /oi A-o?aaiaio oea?eiiaaia eiaeooee?oao eiioi?iaoeeiiiia
oi?ie?iaaiea aeoeaiiai oeaio?a a iieaeoea Glu-ieacieiiaaia.
Eiioi?iaoeeiiiay aeoeaaoeey i?ioa?iaioa i?e acaeiiaeaenoaee n iicaeieie
i?iaeoeoaie aeaa?aaeaoeee oea?eiiaaia/oea?eia iiaeao auoue iaeiei ec
iooae ?aaoeyoeee oea?eiieeoe/aneiai i?ioeana. Aia?aua iieacaii, /oi
DH-aeeia? oea?eia ia?acoao eiiieaen n Glu-ieacieiiaaiii. Iieacaii, /oi
ia ia/aeueiuo yoaiao aeae?ieeca i?e iouaieaiee (N-aeiiaiia ioaeaeueiuo
iieaeoe oea?ei-iiiiia?a oaaee/eaaaony n?iaenoai ieacieia e oea?eio. N
iiyaeaieai O-iieeia?ia i?ioaieeoe/aneia aeaenoaea ieacieia ii ioiioaieth
e oea?eio oae aea, eae e i?e acaeiiaeaenoaee n oea?eiiaaiii,
?aaoee?oaony aeiiieieoaeueiuie eecei-naycuaathueie o/anoeaie.

Eeth/aaua neiaa: oea?ei, X- e E-o?aaiaio oea?eiiaaia, DH-aeeia? oea?eia,
Glu- e Lys-ieacieiiaai, i?ioaieeoe/aneay aeoeaiinoue, aeoeaiue oeaio?.

SUMMARY

Skomorovska-Proquolyt O.V. Effect of fibrinogen/fibrin and their
fragments on Glu-plasminogen properties. – Manuscript.

Thesis for a scientific degree of candidate of biological sciences by
speciality 03.00.04 – biochemistry. – A.V.Palladin Institute of
Biochemistry of the National Academy of Sciences of Ukraine. Kyiv, 1999.

The thesis is devoted to the study of the changes in Glu-plasminogen
properties upon its interaction with fibrinogen/fibrin and their
proteolytic fragments.

Glu- and Lys-plasminogen interactions with native and desAABB-fibrin
obtained from partly degraded fibrinogen were investigated.
Glu-plasminogen is a native form of the proenzyme and Lys-plasminogen is
a partially degraded one that lacks first 77 amino acid residues. It is
found that native fibrin binds 7 times more Lys-plasminogen as compared
to Glu-plasminogen. At the same time, when fibrin is formed from partly
hydrolyzed fibrinogen, the appearance of less than 1% X1-fragments in
the system leads to a 10-fold increase in glu-plasminogen binding, but
the quantity of adsorbed Lys-plasminogen increases only for 5%. The
amount of Glu-plasminogen bound to partly hydrolyzed fibrin reaches the
level of Lys-plasminogen binding. It is found that both, plasminogen
fragment kringle K1-3 containing strong lysine binding site, and
(-aminocaproic acid at concentration saturating this binding site,
inhibit Lys-plasminogen binding to native fibrin. There is no effect
when the native form of proenzyme is used. It is shown that the changes
in sorption properties of Glu- and Lys- forms of proenzyme are
associated not only with the exposure of new plasminogen binding centers
at fibrinogen/fibrin molecule but also with conformational state of the
intact proenzyme molecule. Partly hydrolyzed (to X-fragment state)
fibrin induces considerable conformational changes in intact plasminogen
resulting in Glu-plasminogen transfer to Lys-plasminogen like state and
the interaction with this fibrin is mediated by high affinity binding
site of the native pro-enzyme.

Fibrinogen E-fragment induces the formation of the active center in
Glu-plasminogen by conformational changes upon interaction. During this
interaction in the absence of plasmin and tissue-type plasminogen
activator Glu-plasminogen transforms to a partly degraded form. Both,
Glu-plasminogen complex with soluble fibrinogen E-fragment and the
native proenzyme eluted from immobilized fibrinogen E-fragment are
active towards fibrin and plasmin-specific chromogenic substrate. This
activation of the proenzyme upon interaction with the late degradation
products of fibrinogen/fibrin could be one of the ways of fibrinolytic
process regulation.

The changes in sorption properties of immobilised fibrin DH-dimer as
compared to immobilised fibrinogen D-fragments are observed. The
affinity of fibrinogen DL and DLa-fragments to Glu-plasminogen is much
lower than to Lys-plasminogen, DH-fragment of fibrinogen does not
interact with the native form of proenzyme, while fibrin DH-dimer binds
Glu- as well as Lys-plasminogen. The formation of fibrin DH-dimer
complex with Glu-plasminogen is shown first. Both, Glu-plasminogen and
Lys-plasminogen interactions with DI-dimer are abolished by
(-aminocaproic acid that could be an evidence of plasminogen binding
sites exposure at fibrin D-domain. They are complementary to lysine
binding sites of plasminogen and they are inaccessible to
Glu-plasminogen at fibrinogen molecule.

Complex dissociation constants for native and partly degraded form of
plasminogen with DH-dimer are calculated to be 3.2(10-6 and 3.7(10-6 M,
correspondingly.

It is established that there is an increase of the enzyme affinity
towards the substrate during the plasmin hydrolysis of native and partly
hydrolyzed polymeric fibrin. It is shown that at the beginning stages of
hydrolysis when (C-domains are cleaved from some fibrin monomer
molecules the plasmin affinity to fibrin is increased. This fact allows
concluding that the proteolytic action of plasmin to fibrin with
appearance of X-polymers as well as upon interaction with fibrinogen is
regulated by additional lysine binding sites. The rate of native fibrin
hydrolysis by plasmin formed by t-PA activation of Lys-plasminogen is
twice higher the one of Glu-plasminogen. At the same time, rates became
equal upon hydrolysis fibrin, which is obtained from partly degraded (to
X-fragment state) fibrinogen. So, it could be assumed that X-polymers
are playing a regulatory role in fibrinolytic process.

Key words: fibrin, fibrinogen X- and E-fragment, fibrin DH-dimer, Glu-
and Lys-plasminogen, proteolytic activity, active center.

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