Диссертация (1174184), страница 2
Текст из файла (страница 2)
et al., 2004]..Perticarari S.Fas--,,[Perticarari S., 2008].(sFas)Fas.Fas-(soluble Fas – sFas),. sFas, . .Fas-,-FasFКsL.,ё.36:––()(),.,,-,,..–,-,-.-,,«»,.Д. .FКs-., 2007].,:,Fas-..,,ё-.,,.-.37:-sFas,FasFasL,-sFasFasL.,Д. .., 2007].-sFas1((-)-).-sFas,Дβ005;. .. ..,., 2006]..Fujisawa M.,sFКs27(γ,6±β,4/),/, p=0,0γ)(4,9±β,759(5,1±β,434/, p=0,0β) [Fujisawa M.sFКs2003].-(r=0,5, =0,005).,sFКs(r=0,55, =0,00β).,-sFКs.sFКsL,-.,-sFКs,38FКs-,-.ЭFas-FasL.ee40),TNF-TNF-.Io–,-(oa-aёoFКsLe(CD95L, CD154, CD178) ( oβ5-30%)a,,-TNF--IITNF (oβ0%)ДFКs,FasL.-e(CD8+ , NK-,CD4+ -)«),»a–e,,,,(Fas+)-:(e. FasLFas-., β00βЖ.Faso-a .,.
., 2016].[-,e,11-1γoea.o-,,o,oao,,o.,aa[,. .., 2011Ж.FasL [Francavilla S., 2000],39-,Fas,,.,,gld –FasL.,-Д..., 2002].,-,,,ё -.-,Д. .., 2006]..Riccioli A.FКsL,-,-FКsL-–-[Riccioli A., 2003].,,FКsL,-[Nair R., 2003]..Riccioli A.Fas--,-,FasL,,,FasL –[Riccioli A., 2003].gld,FКsL,,40gld[Riccioli A. et al., 2003].FКs-.,-Fas,().,ёFКsL,gld,,,FКs-A., 2001][Sugihara.,FКsFКsLё.,,, FКsLFКs,.-,FКsL,[Kimmel SG., 2000].,,, FКsL,-FКsДSakkas D. et al., 1999a; Francavilla S. et al., β000Ж.-,,FКsL ДGreen DR. et al., 2001]..Kim S.-K.Fas,-γ[KimS.-K., 2007].,FasL41,--3,.Fas-,FКsFКsLFКs,,FКsL-..Riccioli A.,-FasL:,ββ% (9FasL41)-(n=14),,(-,-) FasL-,-[Riccioli A., 2005].,,,-p55-α (TNF-α),- (TGF- )-.,.,,-,,[DenisonFC.
et al., 1999].FКsL,Fas-,,,[RiccioliA. et al., 2005].42-FasL (sFasL). FasLёFas-.(sFasL)-.,.,-sFasLД..., 2002].sFКsL–(β6-γ5),-FКsL,FКs,.sFКsLT-,FКsL,(.FasL,,FКsL-sFasL)sFКsLFКsL [Knox PG., 2003].FКsLsFКsL,FКs.–,(,),, . .,. ., β007; Brauer PR., 2006].[(-26 –-7 –β),1,-.-MMP-7 (PUMP)-.,,,,MMP-2, MMP -7, TNF-α43,-TGF- ,--FasLsFКsL.,. ., β007].[MMP,-[Wilson CL., 1995Ж.,,,-ДLООЦКЧ MF., 2003],.:;,ё,[Wilson CL. et al., 1995Ж,ДГСКЧР J.
et al., 2002].,.,MMP,ДBЮМСЦКЧ-Shaked O. etal., 2002; Riccioli A. et al., 2005].Riccioli A..-sFКsL(n=41),:(n=14),(,-),(n=1γ)(n=3) [Riccioli A., 2005].44,sFКsL,.MMP– MMP-9(MMP-7)-MMP-β,[Buchman-Shaked O. et al., 2002].sFКsL-.sFasL,sFКsL,,,-sFasL.sFКsL,(sFКsL/: r=0,γγ6; >0,05/: r=0,144;>0,05) [Buchman-Shaked O. et al., 2002; Riccioli A. et al., 2005]..
[Riccioli A., 2005]Riccioli A.,sFasL,,,sFКsL-[Fujisawa M. et al., 2003].,Fas,,FasL,ёFas,.45FasL,1.3.ё,20%-,,«»,TUNEL [Oosterhuis G.J. et al.,2000; Wang X. et al., β00γЖ..Baccetti B.0,1%,–,10%,– 25% [Baccetti B., 1996].ё,2,., Lachaud ..ё,,-,-«swim-up»,[Lachaud., β004].,-«swim-up» Д.
.., β008 ; Almeida C. et al., 2005].,,,,-.,.«swim-up»,,,46-«swim-up».,.2ё«,%n-[Ricci G.,2002]*11,6±1,812,5±2,27,β±1,β7,6±1,11,β±0,61,7±0,810β,78±0,87*7βγ±β,0*23*β,5±1,β1,β±0,7-*1γ,1±7,γ294,1±4,1*1333±3,0*6024,71529*11,0±4,γ-*40,9±14,γ20γ4±4,0*574,5±γ,7*7-AnV+/PI-:*-;TUNEL---4,9±γ,γ28»–[Lachaud., 2004]«sаТЦ-Юp»[TaylorS.L., 2004][SchuffnerA., 2001][Gandini L.,2000][SergerieM., 2005][Ricci G.,2002][SchuffnerA., 2001][Shen H-M.,2002][Gandini L.,2000][SergerieM., 2005][Sion B.,2004][Ricci G.,2002]«sаТЦ-Юp»;47-(«PОrМШХХ»«PЮrОSpОrЦ»).[Gadella B.M. et al., 2002].-,.ooe,asаТЦ-Юp o,ё.
.-[., 2005].,«PЮrОSpОrЦ»(1β%,sаТЦ-Юpё).5,5% [Gandini L. et al., 2004].. .,. ..,90%ё[. ., 2005;. ., 1999Ж..ooe-e-.-,Lachaud.,,[Lachaud.,-β4-in vitro., β004].48γ7°C,(,),,(PI).ё,[Sakkas D. et al., 1999a, 1999b;-Blanc-Layrac D. et al., 2000; Ramos L. et al., 2001],,-,,.,.Lachaud-..-,«»,[Lachaud ., β004].-,β4-..,.,,,..Brugnon F.ё-–-,[Brugnon F., 2006].,,,ё.-49.[.., β015 ; Barroso G. et al., 2000; Aitken R. et al.,2010, 2014]..Sergerie M.,,[Sergerie M., 2005] (( ˂0,001).Donnelly E.T.2),-[Donnelly E.T., 1999].10–15%,Д.
., β01β;. ., β016; Bungum M.,2013; Das M., 2013].. ..,β68% (11,β±β,8%).,: 1γ,β±β,β%( =0,0β) Д8,5±1,1%. ., β015Ж.ДGreco E. et al., β004Ж,,(βγ%4,γ%)..Gandini L.,,(,2000] (( <0,001) [Gandini L.,–2).(n=β8)-() (n=30),11,γ±4,9%,11,γ±4,4%,,)( <0,001).50,. ., β008 ; Agarwal A. et al., 2005].[,.,Bcl-2 –,-–Д ane D.J. et al., 1993],.,(,,).,-.,,,-.,,.,,-ё[Gandini L. et al., 2000].Shen H-M..,,,-V,TUNEL-:-((AnV+/PI–)51)β4,7((AnV+/PI+)-)19,7%,)-,(15,0%) [Shen H-M, 2002].[Oosterhuis G.J. et al., 2000].(r=0,45,<0,01);,(r=0,55, <0,01)(r=0,16),,-–[Shen H-M.
et al., 2002].(,-) [Ricci G. et al., 2002; Chen C-H. et al., 2004; Muratori M. et al., 2008]..,,[Oehninger S., 2003; Wang X. et al., 2003].Д. ., β005;. ., 2014;. ., β015; Sivanarayana T., β01βЖ,,,() ёet al., 2000; Rubes J., 2005].52-[Muratori M..Ricci G.(),,ё,-[Ricci G., 2002].,..(r=0,γ8; <0,01)( nV–/PI–)Durn N.K.-(r= –0,37; <0,01).-.,-[Durn N.K., 2001].) Д(β005;.
.., 2015; Zini F. et al., β010Ж.(Д. ..,-). .., β014;. .., 2015].,,ё,-c[Lee TH. et al., 2010].,()Д.-., β011Ж.,β5–40%-(β0–γ0%),Д. .., 2015; Bungum M. et al., 2013;Evenson D.P. 2013].53,«»,[Benchaib M., 2007]. Buyalos R.,-5-10×106/.97×106/.-165×106-[Buyalos R., 2004].,,,Д-. ., β005;. ., β014;Sivanarayana T., 2012].. ..Д. .2005],.-Д.
.. .,. ., β015Ж.-.,:,,Д-. ., β016Ж.:,Д. ., β015;. ., β016;-. ., β017; Benchaib M.,-2007; Muratori M., 2008].,Д. ., β015; Barroso G., 2000; Oosterhuis G.J., 2000; Giwercman A.,2003; Schuffner A., 2002; Komija A., 2014].,ё[Ramos L., 2001].54,ёGlander H-J.-Oosterhuis G.J.,,:-,,-[Glander H-J.
et al., 1999; Oosterhuis G.J. et al.,2000].-/.,,,--,-«Percoll» [Glander H-J. et al., 1999Ж,ДOosterhuis G.J. et al.,2000].Gandini L..,,:-,;;[Gandini L., 2000].,,):(-,-––.,:,,55«swim-up»,.-,.Gandini L.,ё[Gandini L., 2000].,. .[Singh N.P. et al., 2003],., 2017;[Singh N.P. etal., 2003],..Shen H-M.,-(AnV+/PI+)(r= –0,β5r= –0,28(r= –0,29, <0,05(r=0,59; <0,05,)-r= –0,7, <0,01),(r=0,58r=0,49; <0,01),(r=0,5r=0,48; <0,01),–-r=0,49; <0,01) [Shen H-M., 2002].,(AnV+/PI+)(r=0,56r=0,48, <0,01),<0,01)(r=0,6(r=0,49-r=0,46, <0,01).,(AnV+/PI-).,r=0,γ9,-.
[Shen H-M., β00βЖ,Shen H-M.,ДBarroso G., 2000; Gandini L.et al., 2000; Oosterhuis G.J., 2000].,Д. .Rubes J., 2005].56., 2015; Muratori M., 2000;,,,. ., β015; Borini A., 2006; Tavukcuoglu IS., 2012; Si-[mon L., 2013].[Erenpreiss–J. et al., 2004].(-,.)Дё., β015 ; Evenson D.P., 2013].,,γ0%,,15%,-.:β4%,–15%,– 25–γ0%,–– 15–γ0% [Evenson D.P.et al., 2002].. ., β015;[. ., β016; Benchaib M., 2007; Tesarik J., β004 , β005Ж.-,ё..,,-,.a,o oaoa57-ae,. ., β006;[..
., 2013;., β015 , β015 ; Schlegel P.N., 2005; Giwercman A., 2010;Avendano C., 2011].:,,,-,Д-. .., 2008; Seli E. et al., 2005; Brugnon F. et al., 2006].,,-.1.4.–,ё-,.:(-),.,β001;. .Д. ..,., 2005].ё ,,,.-,:I–:;II–():.58-,Д. .., 2008].ac,c,c.a-,-c,ёc.Fas/FasL.FКsFasL(НОКЭС НШЦОЧ,ёDD),(death-inducingДsignaling complex, DISC),., 2005;. .-.
., β014].I-Fas-[Paasch U., β004 Ж.a-c,,-,.Д. .., 2005; Ishii N., 2007].,oae,[Donnelly E.T. et al., 2000; Marques M. etal., 2014].,-,[O’Connell M. et al., 2002].59aa∆ψm,-,(a-9,c),ё-γ. .,[2014; Peterson Q.P. et al., 2010].l-β,(, Bid, Bak, Bok, Bad, Bcl-xS, Bim, Bik, Blk, Hrk),(Bcl-2, Bcl-XL, Bcl-w,,McU, Bfll),Д. .(., 2005;. ., β014].γ.4.ββ,MEROPS –CD, ID:C14) –-,c(Cysteine ASPartate specificproteASE – CASPASE),[SaidT.M., 2004; Almeida C. et al., 2005].,,(:(-2, -8, -9, -10),-3, -6, -7, -14),,[-. ., β014; Said T.M., 2004].ca-3, -6, -7,––-3, -6, -7.,60ё.
.,[2014; Boosani C.S., 2009; Pop C. et al., 2009; Zhang N. et al., 2012].,,[Weng S-L., 2002;,Paasch U., 2003a; Said T.M., 2004].[Unsain. ., β014],N., 2013;[Marchetti C., 2004; Paasch U., β004 ; Eley A. etal., 2005; Martin G., 2005; Grunewald S., 2007]..Weil M., Tesarik J.[Weil M.,-1998; Tesarik J., 2002],[Desagher S., 2000; Shen H-M. etal., 2002].,--[Weng S-L. et al., 2002; Paasch U.,2003b; Said T.M. et al., 2004].c,[a-a. ., β014; Sermondade N., 2013; Modick H. et al., 2014],.c(a448 ),Д. .,., 2008].,in vitr,-Д. .61., 2005].,(),,-,(-).«»,-,,.,,.,FasTNF-α,FasL-.Д..., β006;. .ё-., 2008].,,(,.) Д. .,,.
.,β01γ;-. ., β01γ;., 2016; Jung J.H., 2014].,–BМХ-β,(γ -(.-20(29)-) –-28-,,II,-,. ., 1999;1995; Fulda S., 1998;-[Pisha E.,. ., β010Ж.-.Paasch U.,β004 Ж.)[Paasch U.,ё,10626060/∆ψm.-9--γ,[Paasch U.,2003a, β004 Ж.,[Costantini P. et al., 2000].,-.,...Paasch U.,(–β0,8 %)∆ψm (–γ7,β %),10-,-∆ψm-60∆ψm() [Paasch U., β004 Ж.-9 (r=0,81, <0,05).1-1∆ψm0,9%.(-9,6%)∆ψm ( >0,05).-9 (+45,5%),-γ110-γ (+β9,β%),ё-963ё(+γ4,β%+γ6,0%,).,-9%10,,1-γ-9; –γ,β %(+γ-3).,ee)aёe(,,oo o.,aPaasch U.. [Paasch U., β004 Ж-,-ДO’Connell M. et al., 2002].,.,,.-.–,,.
.Д., β01β , β01β Ж.-/Д. .,. .., β015Ж.Д., β017].64/-[Paasch U. et al., 2004bЖ,ДDonnelly E.T. et al., 2001; O'Connell. et al.,,2002],-ДGiraud M. N., β000Ж,Д. .., β015Ж.,,-/. .[., β017; Donnelly E.T. etal., 2001; Schuffner A., 2001; Sion B., 2004; Paasch U. et al., 2004b].,∆ψm.∆ψm,,[O’Connell M. et al., 2002; Martin G. et al., 2004; Paasch U. et al.,2004b].ё–:,,AnV–[Glander H-J. et al.,1999Ж,-ДDurn N.K., 2001; Schuffner A., β001Ж,ДSion B. et al., 2004].[Paasch U.