.

Цитогенетичні аспекти розвитку in vitro доімплантаційних зародків ссавців, отриманих біотехнологічними методами: Автореф. дис… д-ра біол. наук / В.Є

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OE?A?INUeEA AEAAeAI?ss AA?A?IEO IAOE

NAEAEOe?EII-AAIAOE*IEE ?INOEOOO

EOCI?OeIA AAEA??E ?AAAIIAE*

OAeE 575:57.089.67:591.32:599

OeEOIAAIAOE*I? ANIAEOE ?ICAEOEO

IN VITRO AeI?IIEAIOAOe?EIEO CA?IAeE?A NNAAOe?A,

IO?EIAIEO A?IOAOIIEIA?*IEIE IAOIAeAIE

03.00.15-aaiaoeea

Aaoi?aoa?ao

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

aeieoi?a a?ieia?/ieo iaoe

Iaeana-1999Aeena?oaoe??th ? ?oeiien.

?iaioa aeeiiaia a ?inoeooo? ?icaaaeaiiy ? aaiaoeee oaa?ei OAAI.

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

Nieiiei Ieaenaiae? Iao?iae/

?inoeooo iieaeoey?ii?
a?ieia?? ?

aaiaoeee IAI Oe?a?ie, i.Ee?a

caa. a?ae. a?io?i?/ii?
aaiaoeee

aeieoi? a?ieia?/ieo iaoe,

i?ioani? Eeeiaiei A’y/aneaa
A?eoi?iae/

?inoeooo oaa?eiieoeoaa OAAI,
i.Oa?e?a

caa. eaa. aaiaoeee ?icaeoeo

aeieoi? a?ieia?/ieo iaoe,

i?ioani? *oo??e Ai?en
Ieeieaeiae/

?inoeooo caiea?ianoaa ?
a?ieia??

oaa?ei OAAI, i.Euea?a

aieiaiee iaoeiaee
ni?a?ia?oiee

I?ia?aeia onoaiiaa: Ee?anueeee iaoe?iiaeueiee
oi?aa?neoao

?i. Oa?ana Oaa/aiea, i.Ee?a

eaoaae?a caaaeueii? oa
iieaeoey?ii?

aaiaoeee

Caoeno a?aeaoaeaoueny “14” o?aaiy 1999 ?. i 10.00 aiaeei? ia can?aeaii?
niaoe?ae?ciaaii? a/aii? ?aaee Ae. 05.15.01 Naeaeoe?eii-aaiaoe/iiai
?inoeoooo OAAI ca aae?anith: 270036, i. Iaeana, Ia?ae?iiieuenueea
aei?iaa, 3.

C aeena?oaoe??th iiaeia iciaeiieoenue o a?ae?ioaoe?
Naeaeoe?eii-aaiaoe/iiai ?inoeoooo OAAI, 270036, i. Iaeana,
Ia?ae?iiieuenueea aei?iaa, 3.

Aaoi?aoa?ao ?ic?neaiee 5 ea?oiy 1999 ?.

A/aiee nae?aoa?

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

eaiaeeaeao a?ieia?/ieo iaoe
Noaieaae/ A.I.

9

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue oaie. Inoaii?i /anii a na?o? a?aeaoaa?oueny oaeaeeee
?icaeoie a?ioaoiieia?e. Aaaeeeaee aeeaae o ?icoi?iiy, aeine?aeaeaiiy
oa ae??oaiiy aaaaoueio ooiaeaiaioaeueieo i?iaeai noaiiaeaiiy oa
?iaeea?aeoaeueiiai ?icaeoeo i?aai?ci?a, io?eiaieo a?ioaoiieia?/ieie
iaoiaeaie, aiinyoue aaiaoeea, ee?oeiia a?ieia?y oa aenia?eiaioaeueia
aia??ieia?y. Nooo?aa cia/aiiy a oeueiio a?aeiioaii? ia? aea/aiiy
iniaeeainoae ?aiiueiai aei?iieaioaoe?eiiai ?icaeoeo nnaaoe?a in vitro oa
in vivo [Aeuaai A.I., 1988; Mason L., 1989; Seidel G.E., 1983].

Aaaaoi ieoaiue ?ai?iaeoeoeaii? a?ioaoiieia??, ye? a?aeia?aaeathoue
??ci? iai?yie aeine?aeaeaiue, caeeoathoueny iac’yniaaieie. Cie?aia,
aaaeeeaiai cia/aiiy iaaoaa? ?ic?iaeaiiy a?eueo ia’?eoeaieo niinia?a
ioe?iee yeino? nia?ie naioe?a n?euenueeiainiiaea?nueeeo oaa?ei. Ia
ee?oeiiiio oa noaee?oeiiiio ??aiyo, a oaeiae ca ??aiai ?icaeoeo i?ney
o?ainieaioaoe?? ?nio? ?noioia ??cieoey i?ae ca?iaeeaie, io?eiaieie in
vivo oa in vitro o aaeeei? ?iaaoi? ooaeiae. Cia/iee ?ioa?an
aeeeeeathoue aeine?aeaeaiiy ia?oaiiaaiaoe/iiai ?icaeoeo iioeeo?a
nnaaoe?a. I?eaa?oathoue oaaao iaaecae/aei? iiaeeeaino? oeia?ieo
aia??ii?a, cie?aia aeey io?eiaiiy iioiinoaa iaoiaeii oae caaiiai
“oeia?iiai” eeiioaaiiy [Modlinski J.A., Karasiewicz J., 1997].
Aaaeeeaa cia/aiiy ia? oaeineiiaeaiiy iaoiae?a io?eiaiiy iiiiceaioieo
aeeciyo o ??cieo aeae?a oaa?ei. Aaaaoiia?oeyth/? iaae?? iia’ycai? ?c
?ic?iaeith e oaeineiiaeaiiyi i?eioeeiiai iiaiai niiniao ?iciiiaeaiiy o
oaa?ei – eeiioaaiiyi ia?anaaeeith yaea? o iicaaaeaio aeaniiai
yaea?iiai iaoa??aeo yeoeaee?oeio aai ceaioo. Oea iio?aao? aea/aiiy
oaeeo ooiaeaiaioaeueieo i?iaeai ye caeaoi?noue aaiiio ??cieo oei?a
ee?oei aei aca?iiae?? c ?aoeei??ioiith oeeoiieaciith, ?ieue oac
ee?oeiieo oeeee?a o ia?ai?ia?aioaaii? o?iiaoeio aeiii?nueeiai
yae?a, cia/aiiy oa?aeoa?enoee oeeoiieano?a aeey oni?oii? ia?anaaeee
yaea?, iiiaeeiia eeiioaaiiy, aieea oeeoiieaciaoe/ii? niaaeeiaino? ia
eeiioaaiiy oa ?i.

Cia/i? iiaeeeaino? aeey aea/aiiy iaeioe/ieo oa i?oioe/ieo
ia?aoai?aiue o?iiaoeio aaiao ? ca?iaee?a, aeine?aeaeaiue aieeao
??cieo oei?a o?iiiniiieo ii?ooaiue ia ?icaeoie aaiao oa aia??ii?a,
ioe?iee a?ieia?/ii? iiaiioe?iiino? iioeeo?a, nia?iaoici?ae?a oa
ca?iaee?a, aeine?aeaeaiue oeyo?a ?icaeoeo ca?iaee?a ??ciiai
iioiaeaeaiiy iathoue oeeoiaaiaoe/i? iaoiaee.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie. ?iaioa
aeeiioaaeanue o a?aeiia?aeiino? c iaoeiai-oaoi?/ieie i?ia?aiaie
?inoeoooo ?icaaaeaiiy ? aaiaoeee oaa?ei OAAI ii caaaeaiiyo:
“?ic?iaeoe iia? iaoiaee ? oaoiieia?? ?iciiiaeaiiy
n?euenueeiainiiaea?nueeeo oaa?ei” 1986-1990 ??. (N aea?ae?a?no?aoe??
01.87.0050462); “?ic?iaeoe iia? a?ioaoiieia?/i? iaoiaee
i?enei?aiiai ?iciiiaeaiiy aenieioe?iieo n?euenueeiainiiaea?nueeeo
oaa?ei” 1991-1995 ??. (N aea?ae?a?no?aoe?? UA01001476P); “Aaeineiiaeeoe
? ai?iaaaeeoe nenoaie canoinoaaiiy iieaeoey?ii-aaiaoe/ieo, a?io?i?/ieo,
o?c?ieia?/ieo ? a?ioaoiieia?/ieo iaoiae?a a naeaeoe??
n?euenueeiainiiaea?nueeeo oaa?ei” 1996-1998 ??. (N aea?ae?a?no?aoe??
0196U016325), a oaeiae aoea i?aeo?eiaia a?aioaie I?i?noa?noaa
Oe?a?ie o ni?aaao iaoee ? oaoiieia?e N 03.05.02/008-93 (1993-1995 ??.),
N 03.05.00/001-94 (1994-1995 ??.) oa N aea?ae?a?no?aoe?? 0198U002131
(1997-1998 pp.).

Iaoa ? caaaeaiiy aeine?aeaeaiue. Iaoith ?iaioe aoei io?eiaiiy
a?ieia?/ii iiaiioe?iieo ca?iaee?a nnaaoe?a a?ioaoiieia?/ieie iaoiaeaie,
aea/aiiy ?o oeeoiii?oieia?/ieo oa?aeoa?enoee, iniaeeainoae ?icaeoeo
in vitro ia ii/aoeiaeo noaae?yo aia??iaaiaco, ioe?iea iaeioe/ieo
? i?oioe/ieo ia?aoai?aiue o?iiinii iioeeo?a ? ca?iaee?a.

Ca?aeii c iaoith aeine?aeaeaiue aoee iinoaaeai? ianooii? caaaeaiiy:

1. Oaeineiiaeeoe niiniae iaea?aeaiiy iiaiioe?iieo aia??ii?a aaeeei?
?iaaoi? ooaeiae in vitro, a oiio /ene? c aeei?enoaiiyi iioeeo?a,
iaea?aeaieo c y?/iee?a aeeaeo aeiii??a.

2. Ia iniia? oai?aoe/iiai iaa?oiooaaiiy ?ic?iaeoe iia? iaoiaee/i?
i?aeoiaee aei “oeia?iiai” eeiioaaiiy o nnaaoe?a.

3. Aea/eoe aieea ??cieo oaeoi??a ia aoaeoeai?noue io?eiaiiy oaeyo i?ney
i?e?io??o?a?/iiai iiae?eo aia??ii?a.

4. Oaeineiiaeeoe iaoiaeeee aioeeaaoe?? ? ia?oaiiaaiaoe/ii?
aeoeaaoe?? iioeeo?a, ia?anaaeee yaea? ca?iaee?a aeey i?aeaeuaiiy
aoaeoeaiino? io?eiaiiy ?aeiino?oeiaaieo ca?iaee?a o e?ie?a oa
aaeeei? ?iaaoi? ooaeiae.

5. Ioe?ieoe noai o?iiaoeio yaea? ca?iaee?a aaeeei? ?iaaoi? ooaeiae
??ciiai iioiaeaeaiiy oa iaoaoaci? ieanoeiee iioeeo?a cieioenoiai
oii’y/ea ? ei??a, nia?i??a aoaay, ia?aoai?aiiy o?iiaoeio i?ney
caie?aeiaiiy in vitro oa aeoeaaoe?? aei ia?oaiiaaiaco
oeeoiaaiaoe/ieie iaoiaeaie.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. Oaeineiiaeai? iaoiaeeee
aeeo/aiiy iioeeo?a c y?/iee?a aeeaeo ei??a oa oaeeoeue i?ae eiio?ieai
oeueo?acaoeo, eoeueoeaoaaiiy ? caie?aeiaiiy in vitro iioeeo?a a?ae
ie?aieo aeiii??a, ui aeicaieeei io?eiaoe 2-6-ee?oeii? ca?iaeee oa
aeanoioeenoe c o??th ae /anoioith, ui ? aeey iioeeo?a, aeeo/aieo c
y?/iee?a caaeoeo oaa?ei. Anoaiiaeaii, ui aeai?aciaa uioeaeiaaa
o?ainaaa?iaeueia ioieoe?y aio?aeueieo oie?eoe?a y?/iee?a aeeaeo
aeiii??a, ia ia?iaeaieo ai?iiiaeueii, ia ciaioo? i?e ianooii?e
ani??aoe?? e?eueeino? i?eaeaoieo aeey ioieoe?? oie?eoe?a i?ioyaii 2
i?nyoe?a, i?ioa iie?auo? ye?noue iioeeo-eoioethnieo eiiieaen?a (IEE)
/a?ac 3-4 acyooy i?ney ii/aoeo aeine?aeo aiane?aeie a?aenooiino?
oi?ioaaiiy aeiaoiai o?ea. Aeyaeaia ?iaeea?aeoaeueia ??cieoey i?ae
aeiii?aie ca na?aaeiueith e?euee?noth iii?oieo ? ani??iaaieo
oie?eoe?a, e?euee?noth ? ye?noth IEE, e?euee?noth io?eiaieo in vitro
2-6-ee?oeiieo ca?iaee?a oa aeanoioeeno. Io?eiai? o?eueiino? i?ney
ia?anaaeee ii?oe-aeanoioeeno, iaea?aeaieo in vitro, a oiio /ene? c
aeei?enoaiiyi OPU-iioeeo?a. Aia?oa o c?euenueeiainiiaea?nueeeo oaa?ei
ia ei?iaao aeiaaaeaia iiaeeea?noue aeoeaaoe?? iioeeo?a aei ia?oaiiaaiaco
ca oiiaith ?ia?aoaaiiy aeae?eaiiy ia?oiai iiey?iiai o?ea oa
o?c?ieia?/iiai aeic??aaiiy iioeeo?a – io?eiai? ia?oa-iiaaiiie aoee
caeaoi? aei ?icaeoeo in vitro i?eiaeii? aei 16-ee?oeiii? noaae??.
Aeiaaaeaia iiaeeea?noue aecia/aiiy noao? aia??iia aaeeei? ?iaaoi?
ooaeiae oeeoiaaiaoe/iei iaoiaeii c aeei?enoaiiyi iaei??? iieiaeiee aai
/aoaa?oeiee. Oaeineiiaeaia iaoiaeeea eeiioaaiiy ca?iaee?a e?iey oa
aaeeei? ?iaaoi? ooaeiae iaoiaeii ia?anaaeee yaea? a aioeeaeiaai?
iioeeoe. Anoaiiaeaii, ui ceeooy ia? “iiieano-aeanoiia?” i?ae ae??th
aeaeo?e/iiai no?oio iiaea a?aeaoaaoenue i?e canoinoaaii? iino?eiiai
no?oio aac aeei?enoaiiy ci?iiiai, ?aeiino?oeiaai? ca?iaeee caeaoi? aei
?icaeoeo in vitro aei noaae?? aeanoioeenoe.

I?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a. ?ic?iaeaiee niin?a
eiiieaenii? ioe?iee caie?aeithaaeueii? caeaoiino? nia?iaoici?ae?a
aoaa?a a oiiaao in vitro aeey aeine?ae?a ii iaea?aeaiith aia??ii?a
aaeeei? ?iaaoi? ooaeiae iica i?aai?ciii iiaea aooe aeei?enoaiee i?e
a?aeai?? aoaa?a aeey ooo/iiai in?iai?iiy. Io?eiaiiy ? ia?anaaeea
iieiaeiie aia??ii?a ai?iaaaeaeai? a i?aeoeeo o?ainieaioaoe?? aia??ii?a,
ui aeicaiey? ?noioii ca?eueoeoe e?euee?noue oaeyo a?ae aeiii??a
aia??ii?a. Iieacaia iiaeeea?noue io?eiaiiy o?eueiinoae i?ney ia?anaaeee
?aoeei??ioai aia??ii?a, iaea?aeaieo in vitro, a oiio /ene? c
aeei?enoaiiyi iioeeo?a, aeeo/aieo c y?/iee?a aeeaeo aeiii??a.

Aeaeaii ?aeiiaiaeaoe?? uiaei io?eiaiiy ye?nieo iieiaeiie
aia??ii?a aaeeei? ?iaaoi? ooaeiae, aecia/aiiy o ieo noaoaaeo
o?iiinii oa o?ainieaioaoe?? ?aoeei??ioai (“Iaoiaee/aneea
?aeiiaiaeaoeee ii iee?ioe?o?ae/aneiio aeaeaieth yia?eiiia e?oiiiai
?iaaoiai neioa”, Eeaa-1991); “?aeiiaiaeaoe?? ii iaea?aeaiith
aia??ii?a aaeeei? ?iaaoi? ooaeiae in vitro”, Ee?a-1998, ye? aoee
?icaeyioo?, noaaeai? ? ?aeiiaiaeiaai? aei ae?oeo iaoeiai-oaoi?/iith
?aaeith Iaoe?iiaeueiiai ia’?aeiaiiy ii ieai?ii?e ni?aa? a
oaa?eiieoeoa?; “I?ia?aia ?icaeoeo eiieo?aioiini?iiiaeiiai
oaa?eiieoeoaa aei 2005 ?ieo. I. I?aei?ia?aia “Iiei/ia neioa?noai”,
Ee?a-1997, yea aoea ?icaeyiooa ? noaaeaia ia ni?eueiiio can?aeaii?
naeoe?? ae?iaieoeoaa ? ia?a?iaee i?iaeoeoe?? oaa?eiieoeoaa
iaoeiai-oaoi?/ii? ?aaee I?in?eueainii?iaeo Oe?a?ie ? OAAI.

Iniaenoee aianie caeiaoaa/a. O/anoue aaoi?a a iaea?aeaii? iaoeiaeo
?acoeueoao?a, aeeeaaeaieo a aeena?oaoe??, noaiiaeoue aeecueei 92%, a
naia: i?iaaaeaii iaeyae ? aiae?c ia?oiaeaea?ae e?oa?aoo?e; c?iaeai?
oai?aoe/i? iaa?oiooaaiiy uiaei eeiioaaiiy o nnaaoe?a; ?ic?iaeaia noaia ?
iaoiaeeea aeeiiaiiy aeine?aeaeaiue; c aeei?enoaiiyi no/anieo
iaoiae?a i?iaaaeai? an? aenia?eiaioaeuei? aeine?aeaeaiiy,
aeieoiaioiaai? i?e?ioioia?ao?yie; aeeiiaii noaoenoe/iee aiae?c
io?eiaiiai oeeo?iaiai iaoa??aeo; iioae?eiaai? iaoa??aee aeine?aeaeaiue.
Ie?ai? o?aaiaioe ?ia?o aoee aeeiiai? ni?eueii c ?ioeie
aeeiiaaoeyie. Aeine?aee ii aeeo/aiith iioeeo?a c y?/iee?a aeeaeo
ei-??a oa oaeeoeue iaoiaeii OPU oa /anoeia aeine?ae?a ii ia?anaaeoe?
yaea? ca?iae-e?a i?iaiaeeeanue ni?eueii ?c ni?a?ia?oieeaie
A?aeae?eo o?c?ieia?? ?iciii-aeaiiy i?ae ea??aieoeoaii i?io. 3.
Nii?iiaa a ?inoeooo? ciioaoi?? (Iieueua).

Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??. Iniiai? iieiaeaiiy ?
?acoeueoaoe aeine?aeaeaiue aeiiia?aeaeenue oa iaaiai?thaaeenue ia:
can?aeaiiyo a/aii? ?aaee ?inoeoooo ?icaaaeaiiy ? aaiaoeee oaa?ei OAAI
(1987-1998 ??.); eii?aeeiaoe?eieo ia?aaeao a ?inoeooo? ?icaaaeaiiy ?
aaiaoeee oaa?ei OAAI (1991-1998 ??.); ia i?aeia?iaeieo oa oe?a?inueeeo
iaoeiaeo ? iaoeiai-i?aeo. eiioa?aioe?yo ? ia?aaeao (1988-1998 ??.), a
oiio /ene? iaoeia?e eiioa?aioe?? “Biotechnologia rozrodu zwierzat
gospodarskich – stan badan oraz mozliwosci praktycznego zastosowania”,
Krakow (Iieueua), 1997; II i?aei. eiioa?aioe?? “Aeei?enoaiiy no/anieo
iieaeoey?ii-aaiaoe/ieo ? a?ioaoiieia?/ieo ?ic?iaie o
aaiaoeei-naeaeoe?eieo aeine?aeaeaiiyo”, Iaeana, 1998.

Ioae?eaoe??. ?acoeueoaoe aeine?aeaeaiue iioae?eiaai? a 1
iiiia?ao??, 24 noaooyo a iaoeiaeo aeo?iaeao. 4 ca??ieeao iaoeiaeo
i?aoeue, 36 iaoa??aeao ? oacao eiioa?aioe?e, 1 iaoiaee/ieo
?aeiiaiaeaoe?yo ? 1 ?aeiiaiaeaoe?yo. Anueiai iioae?eiaaii 67 i?aoeue, c
ieo 20 aac ni?aaaoi??a.

No?oeoo?a ? ianya ?iaioe. Aeena?oaoe?y neeaaea?oueny c anooio, 4
?icae?e?a, aeniiae?a oa i?aeoe/ieo i?iiiceoe?e. Ianya aeena?oaoe?? – 357
noi??iie, a oiio /ene? 40 ?ethno?aoe?e ? 33 oaaeeoe?, nienie
aeei?enoaieo e?oa?aoo?ieo aeaea?ae ioiieth? 494 iaeiaioaaiiy.

IAOA??AEE ? IAOIAeE AeINE?AeAEAIUe

Caaaeueia noaia aeine?aeaeaiue iaaaaeaia ia ?en. 1.

Noia?iaoeyoe?th o naiie cieioenoiai oii’y/ea (Mesokricetus auratus),
ieoae-a?a?eae?a NA6 F1 (BALB/c o C57Bl/6) ? e?ie?a ii?iaee
iiaicaeaiaenueeee a?eee aeeeeeaee ?i’?eoe??th oaa?eiai ANAEE oa eOA.
I?ney ia?iaee eOA naieoeue ieoae ? e?ie?a nia?iaoaaee c naioeyie.

Iioeeoe ei??a oa oaeeoeue io?eioaaee a?ae oaa?ei, caaeoeo ia
i’ynieiia?iao? ? eoeueoeaoaaee a na?aaeiaeu? 199, yea i?noeei
10-20% ?iaeoeaiaaii? oaoaeueii? ne?iaaoee oaeyoe, ONA, eOA,
ano?aae?ieo-17 ? aioea?ioeee ia i?ioyc? 22-24 aiaeei i?e oaiia?aoo??
+38,5oN. *anoeio iioeeo?a ei??a i?ney aeic??aaiiy caa??aaee o 1,5 I
oei?eae? iaai?th i?e +5oN.

Eeiioaaiiy aia??ii?a nnaaoe?a

(oeeoiaaiaoe/iee ? ii?oieia?/iee aiae?c iioeeo?a ? ca?iaee?a)Io?eiaiiy
iieiaeiie ? /aoaa?oeiie ca?iaee?aIaea?aeaiiy ?aeiino?oei-aaieo
NT-ca?iaee?a“Oeia?ia” eeiioaaiiyI?e?io??o?-a?/iee iiae?e
ca?iaee?aIaea?aeaiiy ca?iaee?a

in vivoIaea?aeaiiy aiaeioe/ieo ia?oaiiaaiii?aIo?eiaiiy oao?aiei?ae-ieo
ca?iaee?aIaea?aeaiiy oeia?ieo ca?iaee?aIo?eiaiiy ye?nieo ca?iaee?a in
vitroAioeeaaoe?y iioeeo?aIa?oaiiaaiaoe/ia aeoeaaoe?y

iioeeo?aIa?anaaeea yaea? a oeeoiieanoeIaa??iaeoii?y, aeeo/aiiy ?
aeic??aaiiy iioeeo?a in vitroA?aea?? aoaa?a aeey caie?aeiaiiy iioeeo?a
in vitroIaea?aeaiiy ? aeic??aaiiy

in vitro

OPU-iioeeo?a ?en.1. Caaaeueia noaia aeine?aeaeaiue

Ni?eueio ?ieoaaoe?th iioeeo?a ei??a ? oii’y/ea ?c eaiaoeeoiaaieie iica
i?aai?ciii nia?iaoici?aeaie aoaay i?iaiaeeee a iiaeeo?eiaaiiio
na?aaeiaeu? O??iaea. Eaiaoeeoaoe?th nia?iaoici?ae?a aeeeeeaee ca
aeiiiiiaith ?ic/eio aaia?eio (200 IAe/ie, 15 oa.).

Aeey iaea?aeaiiy i?aia?ao?a iaoaoacieo o?iiinii nia?iaoici?ae?a aoaay
in?iaiai? yeoeaee?oeie oii’y/ea eoeueoeaoaaee i?ioyaii 8 aiaeei o
na?aaeiaeu? A?aa?na, yea i?noeei 0,5 iea/ie eieoeai?aeo. A ?io?e
na??? aenia?eiaio?a iaoaoaci? o?iiiniie nia?i??a aoaay io?eioaaee
i?ney in?iai?iiy iica i?aai?ciii iioeeo?a ei??a, o yeeo iiia?aaeiuei
?iaeoeoaaee aeieoaaiiy yaea?iiai aeic??aaiiy.

Iao??o?a?/io o?ainaaa?iaeueio ioieoe?th ai?noo aio?aeueieo
oie?eoe?a y?/iee?a aeeaeo ei??a oa oaeeoeue cae?enithaaee i?ae
eiio?ieai oeueo?acaoeo (ovum pick-up – OPU) aea?/? ia oeaeaeaiue
(/a?ac 3-4 aei?) i?ioyaii 2 i?nyoe?a c aeei?enoaiiyi niaoe?aeueiiai
iaeaaeiaiiy – oeueo?acaoeiaiai neaia?a c i?oaiaei o?ainaeona?ii (oei
Picker, iiaeaeue CS 9100 c /anoioith 6,5 IAoe), ii?aeiaiei c
ani??oth/ei i?eno?i?i (iiaeaeue Mariensee), ?icoaoiaaiei o
aaa?iaeueiiio ciiae? c ianaaeeith aeey ioieoe??, a oaeiae aaeooiii?
iiiie. Ai?iiiaeueio ia?iaeo oaa?ei ia i?iaiaeeee.

E??ieiina?aoaaiiy 7-8-aeaiieo aeanoioeeno aaeeei? ?iaaoi? ooaeiae,
iaea?aeaieo iica i?aai?ciii, iaoiaeii a?o?eo?eaoe??
cae?enithaaee o ?ic/ei? AON (40% aoeeaiae?eieth, 18% o?eieo 70 ? 0,3
I naoa?ice a PBS c 20% oaoaeueii? ne?iaaoee oaeyoe), iienaiiio
I.Eana? aeey a?o?eo?eaoe?? aia??ii?a ieo? [Kasai M. e.a., 1990].

Ia?oaiiaaiaoe/iee ?icaeoie iioeeo?a ei??a ?iaeoeoaaee 7%-iei ?ic/eiii
aoaiieo 7 oa. a PBS c 20% oaoaeueii? ne?iaaoee oaeyoe i?e 37,5oN. A
aeayeeo aenia?eiaioao a na?aaeiaeua eoeueoeaoaaiiy iioeeo?a
aeiaeaaaee oeeoioaeacei D a eiioeaio?aoe?? 1 a/ie.

Ca?iaeee ieoae eoeueoeaoaaee iica i?aai?ciii i?ioyaii 90 aiaeei o
na?aaeiaeu? I16 i?e 37oN, ca?iaee?a e?ie?a – o na?aaeiaeu? Iaiaci A2 c
ianooiiei aeiaeaaaiiyi 20% oaoaeueii? ne?iaaoee oaeyoe ia noaae?? ii?oee
i?e 38,5oN, ca?iaeee aaeeei? ?iaaoi? ooaeiae – i?e 38,5oN a na?aaeiaeu?
199 c oaoaeueiith ne?iaaoeith oaeyoe ia iiiioa?? ai?oae?aeueieo ee?oei
yeoeai?iaiae?a ei??a. Aeey iaea?aeaiiy i?aia?ao?a iaoaoacieo o?iiinii
aia??iie aaeeei? ?iaaoi? ooaeiae, iaea?aeai? iica i?aai?ciii,
eoeueoeaoaaee i?ioyaii 5 aiaeei a na?aaeiaeu? c 0,05 iea/ie
eieoeai?aeo.

Neeyi? i?e?i?ino?oiaioe aeaioiaeyee ia i?e?ieoci? oeio “IE”, iaoaeaa?
iiae? – c e?iiee naieo oiieeo a?eoaaieo eac.

A aeine?aeaeaiiyo ii eeiioaaiith aia??ii?a iaoiaeii ia?anaaeee yaea?
aioeeaaoe?th iioeeo?a, ia?aiin aeanoiia??a o ia?ea?oae?iiaee i?ino??
yeoeaee?oei oa ia?anaaeeo yaea? a oeeoiieanoe cae?enithaaee ca
iaoiaeii, iienaiei ?ai?oa [Chesne P. e.a., 1993] c aeayeeie
iiaeeo?eaoe?yie. Ceeooy ia? “iiieano-aeanoiia?” cae?enithaaee a
iaaeaeo?ie?oiiio 0, C I ?ic/ei? iai?oieo, yeee i?noea 0,1 iI MgSO4
oa 0,05 iI NaNl2 a neeyi?e eaia?? c a?aenoaiith i?ae
ia?aeaeueieie aeaeo?iaeaie 500 i. Aeey i?ae?aooieo e?eueeino? yaea? oa
aiae?co ?o noaio aeaye? ?aeiino?oeiaai? aia??iie oa?aoaaee ?ic/eiii
aa?aieea Oaeno 33342 (5 a/ie) aai aiooaaee nooiiia?o?yi? i?aia?aoe
ca?iaee?a c ianooiiei oa?aoaaiiyi 2%-iei ?ic/eiii aa?aieea A?ica.

C iaoith aea/aiiy aeeiai?ee iaeioe/ieo oa i?oioe/ieo
ia?aoai?aiue o?iiaoeio, aeyaeaiiy oa ?aeaioeo?eaoe?? oei?a
o?iiiniiieo ii?ooaiue, ioe?iee ca?iaee?a aiooaaee nooiiia?o?yi?
i?aia?aoe ca iaoiaeii A.E.Oa?eianueeiai [Tarkowski A. E., ?966].

Iaoa??ae aeieoiaiooaaee i?e?ioioia?ao?yie. Noaoenoe/io ia?iaeo
iaea?aeaieo aeaieo i?iaiaeeee c aeei?enoaiiyi e?eoa???a No’thaeaioa
oa 2-eaaae?ao [Eaeei A.O., 1990], a oaeiae i?eeeaaeieo i?ia?ai aeey
i?e?ieaeueeoeyoi?a “Aeaeo?ii?ea IE-52” [Iieoiai TH.I., 1988].

?ACOEUeOAOE AEANIEO AeINE?AeAEAIUe OA ?O IAAIAI?AIIss Iaea?aeaiiy
aia??ii?a aaeeei? ?iaaoi? ooaeiae c aeic??eeo

iica i?aai?ciii oa caie?aeiaieo in vitro iioeeo?a ei??a

Aeey ?ic?iaee iaoiae?a eeiioaaiiy o aaeeei? ?iaaoi? ooaeiae aeoaea
aaae-eeaei ? iaea?aeaiiy a?ieia?/ii iiaiioe?iieo aia??ii?a ?
aeic??eeo iioeeo?a.

C iaoith a?aeai?o aoaa?a aeey io?eiaiiy ca?iaee?a aaeeei? ?iaaoi?
ooaeiae iica i?aai?ciii iaie i?iaiaeeeenue aenia?eiaioe ii aecia/aiith
aoaeoeaiino? ioe?iee caie?aeithaaeueii? caeaoiino?
nia?iaoici?ae?a aoaa?a ca aeiiiiiaith aaoa?i- ? aiiieia?/iiai
oano?a. Aeine?aeaeaiiy iieacaee a?aenooi?noue a??ia?aeii? ??cieoe? ca
/anoioith iaiao?aoe?? yeoeaee?oei cieioenoiai oii’y/ea
nia?iaoici?aeaie iaio aoaa?a i?ioyaii 5 aiaeei, i?ioa, aoea aeyaeaia
??cieoey i?ae aoaayie i?e iaiao?aoe?? aiiieia?/ii? i?ici?i? iaieiiee
iioeeo?a, ye? caa??aaeenue o nieueiaiio ?ic/ei? (?en. 2), ui
a?aeiia?aeaea ??cieoe? ca /anoioith caie?aeiaiiy ? ae?iaeaiiy iioeeo?a
ei??a.

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00001b048e01fd007a01d6000700000016048c01f9007b01d900040000002d0108000500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?en.2. Ii??aiyiiy caie?aeithaaeueii? caeaoiino? nia?iaoici?ae?a aeaio

aoaa?a in vitro. Ii in? aanoeen – e?euee?noue
in?iaiaieo

yeoeaee?oei (b:c – P 0,05). A?eueoa oiai, e?euee?noue ye?nieo
iioeeo-eoioethnieo eiiieaen?a a iaoeo aeine?aeao /a?ac 3-4 acyooy
a?ae ii/aoeo aeei?enoaiiy oaa?ei ca?eueooaaeanue. Oea iia’ycaii c
oei, ui aeai?aciaa aeeo/aiiy iioeeo?a ia oeaeaeaiue c ?ioa?aaeii 3-4
aei? ia?aoeiaeaea? a?aeai?o oa ?icaeoeo aeii?ioth/iai oie?eoea,
aiane?aeie oiai a?aenooiy iaoeyoe?y, oeeee?/i?noue i?eieiy?oueny
[Gibbons J.R. e.a., 1994; Kruip T.A.M., 1994].

Iao? aenia?eiaioe iieacaee, ui i?ae aeiii?aie-oaeeoeyie ?nio?
?iaeea?aeoaeueia ??cieoey o na?aaei?e e?eueeino? iii?oieo ?
ani??iaaieo oie?eoe?a, e?eueeino? aeeo/aieo iioeeo?a, a oiio /ene?
i?eaeaoieo aeey eoeueoeaoaaiiy, 2-6-ee?oeiieo ca?iaee?a oa
aeanoioeeno, io?eiaieo c oeeo iioeeo?a (oaae. 4).*anoioa ae?iaeaiiy
caie?aeiaieo in vitro OPU-yeoeaee?oei (83/113, 73,5%) oa ?icaeoeo
oaeeo ca?iaee?a iica i?aai?ciii aei noaae?? aeanoioeenoe (18/106,
17,0%) aoea iaioa, i?ae o eiio?ie? (iioeeoe, aeeo/ai? c
?cieueiaaieo y?/iee?a caaeoeo oaa?ei) – 78/95, 82,1% ? 25/95, 26,3%
a?aeiia?aeii, ui a?aeiia?aea? aeaiei ?ioeo aaoi??a [Bungartz L.
e.a., 1995; Palma G.A. e.a., 1996; Rath D., 1993; Smorag Z. e.a., 1997].
Iaeiae, a iaoeo aeine?aeao oey ??cieoey aoea iaa??ia?aeiith ?
iaea?aeai? iaie iieacieee aoee aeu?, i?ae o ?ioeo aeine?aeiee?a.

Aacia?a/ii, iaeiei c aaaiieo /eiiee?a a??oiai ?icaeoeo
caie?aeiaieo in vitro OPU-yeoeaee?oei ? a?aenooi?noue o ieo /anoeie
eoioethno, oiio ui o ei??a ee?oeie eoioethno iathoue aaeeea cia/aiiy ia
o?eueee aeey yaea?iiai, aea ? aeey oeeoiieaciaoe/iiai aeic??aaiiy, yea
iaiao?aeii aeey oi?ioaaiiy /ieia?/iai i?iioeeaona ? ?aiiueiai
aia??iiaeueiiai ?icaeoeo [Konishi M. e.a., 1996]. Ie aaaaea?ii, ui
?ioei /eiieeii a??oiai ?icaeoeo yeoeaee?oei oa aia??ii?a ? oa,
ui OPU-iioeeoe aeic??aathoue oa caie?aeiththoueny, a a
iiaeaeueoiio ? ?icaeaathoueny ie?aii aai a iaeeo a?oiao, oiae? ye
iioeeoe, aeeo/ai? c y?/iee?a caaeoeo oaa?ei ? io?eiai? c ieo ca?iaeee
eoeueoeaothoueny o aaeeeeo a?oiao, oiaoi iia’ycaii c iaaeinoaoiueith
e?euee?noth aooie?eiieo ? ia?ae?eiieo oaeoi??a ?inoo.

13

Oaaeeoey 4

Aieea aeiii?a ia e?euee?noue io?eiaieo OPU-iioeeo?a oa /anoioo
oi?ioaaiiy aia??ii?a in vitro

i?e canoinoaaii? oeneo 0,1 oa 0,2 A

IieacieeeE?euee?noueAeiii?eacyoo?a464540414243E?euee?noue ani??iaaieo
oie?eoe?a, I m

E?euee?noue aeeo/aieo iioeeo?a, I m

E?euee?noue iioeeo?a, i?eaeaoieo aeey aeic??aaiiy in vitro, Im

E?euee?noue iioeeo?a, in?iaiaieo in vitro

*anoioa oi?ioaaiiy 2-6-ee?oeiieo ca?iaee?a (aeaiue 2, %)

*anoioa oi?ioaaiiy aeanoioeeno (%)10

10

10

10

10

9e3,90,41a

(n=77)

0,90,13ab

(n=17)

0,60,11ac

(n=12)

12

10/12

(83,3)

1/11

(9,1)2,90,24bd

(n=58)

1,20,25ab

(n=24)

0,70,18ab

(n=14)

14

9/14

(64,3)

2/13

(15,4)2,90,26bc

(n=57)

0,80,22ab

(n=16)

0,60,18bc

(n=11)

11

5/11

(45,5)

1/10

(10,0)3,40,27ab

(n=68)

1,50,34a

(n=29)

1,30,32b

(n=25)

25

20/25

(80,0)

4/23

(17,4)2,20,24c

(n=43)

0,70,17b

(n=13)

0,60,17bc

(n=12)

11

9/11

(81,8)

2/10

(20,0)2,60,18cd

(n=51)

0,70,19b

(n=14)

0,50,14ac

(n=9)

9

6/9

(66,7)

0/8

(0) a – a iaeiiio aeine?ae? eoeueoeaoaaiiy aia??ii?a aei noaae??
aeanoioeenoe ia cae?enithaaee

16

O iaoeo aeine?aeaeaiiyo iiaiioe?iia aeic??aaiiy OPU-iioeeo?a
aeinyaaeinue o?eueee o i?enooiino? aeiaeaoeiai? e?eueeino? a?aioeueice,
yeo io?eioaaee ye c oie?eoe?a aeeaeo aeiii??a (?acii c iioeeoaie), oae
? c oie?eoe?a y?/iee?a caaeoeo oaa?ei.

I?ney o?ainieaioaoe?? 10 oaeeoeyi-?aoeei??ioai 10 i?ci?o
ii?oe-aeanoioeeno, io?eiaieo in vitro c aeei?enoaiiyi
OPU-iioeeo?a, o aeaio oaeeoeue aoea ca?a?no?iaaia o?euei?noue.
I?ioyaii 2-i?ny/iiai ia??iaeo aeine?ae?a o 6 iino?eieo aeiii??a ie
ia niinoa??aaee iaaaoeaiiai aieeao o?ainaaa?iaeueii? ani??aoe?? ai?noo
oie?eoe?a ia noai y?/iee?a, iaoee oa i?oae oaa?ei, ia ca?a?no?iaaii
caoai?thaaiue noaoaaiai aia?aoo, ui a?aeiia?aea? aeaiei ?ioeo
aeine?aeiee?a [Bucher P. e.a., 1996; Kruip T.A.M. e.a., 1994].

Aoaeoeai?noue a?o?eo?eaoe?? aeanoioeeno aaeeei? ?iaaoi? ooaeiae,
io?eiaieo in vitro, a ?ic/ei? AON i?e 1-nooiaiaa?e aea?e?a?aoe??
caeaaeaea a?ae noaae?? ?o ?icaeoeo – aeey 7-aeaiieo aeanoioeeno iaea
i?noea oaiaeaioe?y aei i?aeaeuaiiy /anoioe aeaeeaaiino?
(?aaeniain?? ii?iaeieie i?ney a?o?eo?eaoe?? oa a?aeoaaaiiy) o
ii??aiyii? c 8-aeaiieie (?en. 3), i?e oeueiio eeoa i?ney
1,5-oaeeeiiiai ia?aaoaaiiy a AON-?ic/ei? 7-aeaii? aeanoioeenoe
?icaeioeenue aei noaae?? aeeoieaiiy c i?ici?i? iaieiiee.

picscalex109010009000003ee0b00000900490000000000050000000902000000000500
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2701ffff050000000b022c10b0ff030000001e00050000000102ffffff00050000000902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8b060500000013024506d50605000000140249078b060500000013024907d50605000000
14024d088b060500000013024d08d50605000000140251098b060500000013025109d506
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580bd5060500000014025c0c8b060500000013025c0cd506050000001402600d8b060500
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14021904460b0500000013026304460b0500000014021904dc0f0500000013026304dc0f
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6304081908000000fa0200000000000000000000040000002d010500040000002d010300
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ffffff0005000000090200000000070000001604100424196a0ea006040000002d010500
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00001604100424196a0ea006040000002d010500040000002d010400040000002d010300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1e00040000002d010100040000002d010600040000002d010700050000000102ffffff00
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a6ff441d3610a4ff0400000004010d00040000000201010009000000320ad40488050100
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3930900090000c000000320afa0e68040300000031303000900090009000040000002d01
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2d010200040000002d010600040000002d010700050000000102ffffff00050000000902
00000000070000001604b0ff381d2c10b0ff040000002d010500040000002d0104000400
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441d3610a4ff0400000004010d00040000000201010009000000320a5c03680601000000
300090000c000000320a5c03920a03000000312e350090004800900009000000320a5c03
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2701ffff030000001e00040000002d010100040000002d010600040000002d0107000500
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0500040000002d010400040000002d010300040000002701ffff030000001e0004000000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?en. 3. Aieea o?eaaeino? aea?e?a?aoe?? ia aeaeeaai?noue 7- ? 8- aeaiieo

aeanoioeeno aaeeei? ?iaaoi? ooaeiae, iaea?aeaieo

iica i?aai?ciii, i?ney ?o a?o?eo?eaoe??

Aeainooiaiaaa aea?e?a?aoe?y 8-aeaiieo aeanoioeeno, oaeeo, ui
?icoe?ththoueny, ? ?icoe?aieo iie?auoaaea aeaeeaai?noue aia??ii?a o
ii??aiyii? c 1-nooiaiaaith aea?e?a?aoe??th – i?ney a?o?eo?eaoe?? o
66,7% aeanoioeeno niinoa??aaeanue ?aaeniain?y ii?iaeieie ? o 33,3% –
aeeoieaiiy c iaieiiee. I/aaeaeii, e?auith ? 2-nooiaiaaa
aea?e?a?aoe?y, ui caaacia/o? aeinoaoi? i?iieeiaiiy e??ii?ioaeoi?a o
aeanoioeaeue ? caiia?aa? ooai?aiith aioo??oiueiee?oeiiiai eueiaeo,
a ianooiia ei?ioei/ania ia?aaoaaiiy o ?ic/ei? AON cieaeo? oiene/iee
aieea e??ii?ioaeoi?a.

Oeeoiaaiaoe/iee aiae?c ia?oaiiaaiaoe/iiai ?icaeoeo

iioeeo?a ei??a in vitro

Ia?oaiiaaiaoe/ia aeoeaaoe?y iioeeo?a ? nooo?aith /anoeiith
oaoiieia?? ia?anaaeee yaea? oa i?e?io??o?a?/iiai caie?aeiaiiy in
vitro o nnaaoe?a [Goto K e.a., 1994; Takahashi S. e.a., 1996].

Oeeoiaaiaoe/iee aiae?c nooiiia?o?yieo i?aia?ao?a aeyaea, ui a iaoeo
oiiaao iioeiaeueiith o?eaae?noth aeic??aaiiy iioeeo?a ei??a iica
i?aai?ciii aeey ?o aeoeaaoe?? aei ia?oaiiaaiaco c a?aooaaiiyi
oaeoi?a o?iiiniiieo ii?ooaiue (aeaaaia?aoe?y ? aeani??ae?caoe?y
o?iiinii, aeie aiaoace I, /anoeiaa ia?icoiaeaeaiiy a?aaeaio?a ia
oi?aaeaioe) aeyaeeinue 30-aiaeeiia eoeueoeaoaaiiy o ii??aiyii? c
eoeueoeaoaaiiyi i?ioyaii 24, 36 ? 42 aiaeei. A iaoeo aeine?aeao
ia?oaiiaaiaoe/ia aeoeaaoe?y iioeeo?a ei??a aoea oni?oii ?iaeoeiaaia
aoaiieii ye /a?ac 24 aiaeeie eoeueoeaoaaiiy, oae ? i?ney
ianooiiiai 6-aiaeeiiiai eoeueoeaoaaiiy (noa??iiy), oiaoi /a?ac 30
aiaeei aeic??aaiiy. Ia a?aei?io a?ae aeaieo ?ioeo aaoi??a
[Minamihashi A. e.a., 1993] iaie ia aoei a?aei?/aii a??ia?aeii?
??cieoe? i?ae oeeie aeaiia a?oiaie ca /anoioith aeoeaaoe?? iioeeo?a
(49/89, 55,1% ? 74/107, 69,2% a?aeiia?aeii), aea ?iaeoeoe?y iioeeo?a
ei??a aoaiieii i?ney 30-aiaeeiiiai aeic??aaiiy aeicaieeea io?eiaoe
cia/ii a?eueoa 2-4-ee?oeiieo ia?oaiiaaiii?a (55/107, 51,4%), i?ae
ia?iaea ee?oei /a?ac 24 aiaeeie (13/89, 14,6%). Iiaeaeueoa
eoeueoeaoaaiiy ia?oaiiaaiii?a i?eaiaeeei aei ?o ?icaeoeo aei noaae??
8-16 aeanoiia??a (18/107, 16,8% ? 6/89, 6,7% a?aeiia?aeii).

Oeeoiaaiaoe/iee aiae?c ia?oaiiaaiaoe/ieo aia??ii?a aeyaea iaya-i?noue
?ioa?oacieo ? i?ioacieo ii?oieia?/ii ii?iaeueieo yaea? aeanoiia??a,
iaoaoaci? ieanoeiee ca?iaee?a i?noeee ye aaiei?aeiee, oae ? aeeiei?aeiee
iaa?? o?iiinii. A?eueo?noue 2-ee?oeiieo ca?iaee?a iaea ia?oa iiey?ia
o?eueoea.

Iniaeeaee ?ioa?an aeeeeeathoue aenia?eiaioe ii aeoeaaoe?? iioeeo?a
nnaaoe?a aei caaa?oaiiy ia?oiai (?aaeoeoe?eiiai) ae?eaiiy iaeico,
oiio ui oea iiaea “iaaeeceoe ae??oaiiy ieoaiiy i?i aiaeioe/iee
ia?oaiiaaiac nnaaoe?a” [Aeuaai A.I., 1988]. A iaoeo aenia?eiaioao
?iaeoeoe?th iac??eeo iioeeo?a ei??a i?iaiaeeee c aeei?enoaiiyi
i?aeoiae?a, cai?iiiiiaaieo ss.Eoayeii aeey aeoeaaoe?? oao?aiei?aeieo
ieoa/eo iioeeo?a – iaea?aeai? aaoi?ii aiaeioe/i? ia?oaiiaaiaoe/i?
aeanoioeenoe aoee aaiaoe/ii ?aeaioe/i? iaeia iaei?e oa ?oi?e iaoa??
[Kubiak J. e.a., 1991].

Aeine?aeaeaiiy i?iaiaeeee ia iioeeoao ei??a 3 a?oi a caeaaeiino? a?ae
o?eaaeino? ia?iaee oeeoioaeaceiii D (oaae. 5). Ia?aae ia?iaeith
aoaiieii o a?eueoi? /anoeie oeeo iioeeo?a ia aoei aeyaeaii
iiey?ieo o?eaoeue (Ae1 ? Ae2), ?aooa iioeeo?a i?noeee ia?oa iiey?ia
o?ei (Ae3). Aenia?eiaioe iieacaee, ui aeoeaaoe?y iioeeo?a i?e
iaio?e o?eaaeino? ae?? oeeoioaeaceio D (a?oia Ae2) aoea cia/ii
oni?oi?oith, i?e oeueiio, ye iieacaa oeeoiaaiaoe/iee aiae?c
i?aia?ao?a yeoeaee?oei 57,1% (12/21) iioeeo?a aaciina?aaeiuei
ia?aae canoinoaaiiyi aoaiieo aoee ia noaae?? oae caaiiai “aeieo
aiaoace ?” (oiaoi aiie iaee o?iiiniiiee iaa??, yeee neeaaeaany c
60 oi?aaeaio?a).

Oaaeeoey 5

Aeoeaaoe?y iioeeo?a ei??a aoaiieii i?ney ?ia?aoaaiiy

aeae?eaiiy ia?oiai iiey?iiai o?eaa

A?oiaO?eaae?noue AnueiaiE?euee?noue (%) ia?oaiiaaiii?aaeine?aeoia?iaee
oeeoioa-iioeeo?aaeoeaiaaieo2-4-ee?oeiieo5-16-ee?oeiieoeaceiii D
(aiae.)yeoeaee?oeica?iaee?aca?iaee?aAe18255 (20,0)1 (4,0)1 (4,0)Ae252817
(60,7)8 (28,6)3 (10,7)Ae3580 (0)0 (0)0 (0)a – iioeeoe aeic??aaee in
vitro i?ioyaii 24 aiaeei, inoaii? 4 aiaeeie – o

a?aenooiino? oeeoioaeaceio

Ioaea, aeiaeaaaiiy aei na?aaeiaeua aeic??aaiiy iioeeo?a ei??a
oeeoioaeaceio D i?ney ?o 15-aiaeeiiiai aeic??aaiiy in vitro, oiaoi
i?eaeecii ca 3 aiaeeie aei ?aaeoeoe?eiiai ae?eaiiy iaeico o a?eueoino?
iioeeo?a, aeinoaoi? aeey i?eai?/aiiy aeae?eaiiy ia?oiai iiey?iiai
o?eueoey. I?ney ia?iaee aoaiieii 60,7% yeoeaee?oei a oe?e a?oi?
aeyaeeenue aeoeaiaaieie – ia?aaoaaee ia noaae?? oaeioace II iaeico c
aeaiia aeeiei?aeieie iaai?aie o?iiaoeae aai i?noeee iaeei /e aeaa
ae?ii/? i?iioeeaone. Aiae?c nooiiia?o?yieo i?aia?ao?a 2-16-ee?oeiieo
aia??ii?a iieacaa, ui aeanoiia?e ia?oaiiaaiaoe/ieo ca?iaee?a iaee
yae?a, e?euee?noue yeeo a?aeiia?aeaea e?eueeino? aeanoiia??a, a
yae?a i?noeee yaea?oey.

Ne?ae a?aei?oeoe, ui ia?iaeai? oeeoioaeaceiii iioeeoe, ye?
aeae?eeee ia?oa iiey?ia o?eueoea ia?aae ia?iaeith aoaiieii ia iaee
iciae aeoeaaoe??.

Oaeei /eiii, iaie aia?oa aoea iieacaia iiaeeea?noue
ia?oaiiaaiaoe/iiai ?icaeoeo iioeeo?a n?euenueeiainiiaea?nueeeo oaa?ei
(ei??a) ca oiiaith ?ia?aoaaiiy aeae?eaiiy ia?oiai iiey?iiai o?eueoey oa
aeoeaaoe?? iioeeo?a ia noaae?? aeic??aaiiy, yea ca /aniaeie
ia?aiao?aie a?aeiia?aea? o?c?ieia?/i?e c??eino? iioeeoa i?ney 24
aiaeei eoeueoeaoaaiiy, ui ? aeoaea aaaeeeaei aeey ianooiiiai ?icaeoeo.

A?aenooi?noue ia?oiai iiey?iiai o?eueoey ia oie /an, eiee a ii?i? o
iioeeo?a ei??a aaea a?aeaoaa?oueny aeaaoe?eia ae?eaiiy iaeico i?ney ?o
aeoeaaoe?? nia?iaoici?aeii aai ?ioei oaeoi?ii (/a?ac 24 aiaeeie
aeic??aaiiy), iayai?noue oao?aiei?aeieo iioeeo?a ia noaae?? aeieo
aiaoace I c ii?oieia?/ii ii?iaeueieie o?iiiniiaie a iaio iaai?ao,
iioeeo?a c aeaiia aeeiei?aeieie iaai?aie o?iiaoeae aeicaiey?
i?eionoeoe, ui i?eiaeii? aeaye? iioeeoe a iaoeo aeine?aeao
?icaeaaeenue ca aiaeioe/iei oeyoii.

Noai?aiiy oeia?ieo aia??ii?a oa ia?niaeoeae

?o aeei?enoaiiy a eeiioaaii? ca?iaee?a

Aenia?eiaioe iieacaee (oaae.6), ui i?ney ca?eueiaiiy a?ae i?ici?i?
iaieiiee aa?aaaoe?? i?ci?o ii?oe aaeeei? ?iaaoi? ooaeiae, io?eiaieo
in vivo, oa iieiaeiie i?ci?o ii?oe iiaeia oni?oii aeinyaoe
iaoai?/iei i?eoeniaiiyi ?o iaeei aei iaeiiai a ?ic/ei?
o?oiaaiaaethoeieio, i?e oeueiio /anoioa oi?ioaaiiy aa?aaao?a i?ae
ia?aie oe?eeo aia??ii?a oa ia?aie ye?nieo iieiaeiie a??ia?aeii ia
a?ae??ciyeanue. A?eueoa i?ae o 2 ?ace aoaeoeai?oei aeyaeany niin?a
io?eiaiiy aa?aaao?a aaaaeaiiyi aeaio iieiaeiie a ionoo i?ici?o
iaieiieo aac aeei?enoaiiy OAA, ui caaacia/o? u?euei? eiioaeoe oa ?o
caa?aaeaiiy ? aaeaac?th i?ae aia??iiaie.

Oaaeeoey 6

*anoioa oi?ioaaiiy oeia?ieo aia??ii?a

Anueiai ia?E?euee?noue (%)Niin?aAa?aaaoeaia??ii?a aaiaa?aaao?a oeia?ieo
aeanoioeenoaa?aaaoe??iieiaeiiei?ney eoeue-a?ae
aeo?aeieoa?aeoeaoaaiiyia?aa?aaao?aIaoai?/ia

aa?aaaoe?y“aia??ii-

aia??ii”2812a (42,9)9a (32,1)9c (75,0)Iaoai?/ia

aa?aaaoe?y“iieiaeiea-

iieiaeiea”3714a (37,8)10a (27,0)10c (71,4)?ici?uaiiy a i?ici?o
iaieiieo“iieiaeiea-

iieiaeiea”5144b (86,3)37b (72,6)37c (84,1) a:b – P

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