Диссертация (1174184), страница 6
Текст из файла (страница 6)
.., 1990],.-19.1–,A a oeoa0,5β, γ, 4oa a o(80100/); β–.o oeea a a. O aooo e o e– 80/ .191; γ–; 4–oe oe eeao oe.eaa№e oCeeaa o eeaooe,o-.. . Д. .., 1990],,-,1.-1.-6155000 g–30°.800,0,.β.10 M-HCl1:1(pH 7,4)70°γ0-.40-4510000 g,-...3.ё).(50%β-410000 g60(-HCl=7,4).4..-HCl(1,5 1β,)-ё1.,,--HCl0,1675192,,-=9,0.ё(7%(1β).-20).,-2-.20.–;–-3.6.2.2. Иin vitroin vitroё–.,193-,: 0,16Chlamydia trachomatis; 60/;1/ STSβ004/26-β2-.(Sigma,).,-20.250/6(1)-(AЧV+/PI–)-)(( >0,05) (49).,250/6Chlamydia trachomatis (0,13),-.+/Chlamydia trachomatis (,γ)(AЧV+/PI–)-β,6Chlamydia trachomatis(2) ( ˂0,02),(AЧV+/PI–)1( >0,05).61/ STS (5),+ STS (5).,(AЧV+/PI–)-1,9-STS194(4) ( ˂0,02),(AЧV+/PI–)1( ˂0,02).49(AnV+/PI–)-(M (in vitro25;75);n=20)(AЧV+/PI–)-((((9,0 (6,9; 9,9))2C.
trachomatis)3+C. trachomatis)4( STS)5(+ STS)6()7(+ )8( 2 2)9(+ 2 2)<0,0β; *(STS)9,4 (7,9; 10,1))1C. trachomatis);9,0 (6,8; 10)26,2 (24,8; 29,0)*#24,0 (20,0; 29,3)*10,0 (7,8; 12,3)44,5 (38,8; 50,8)*23,5 (18,8; 26,5)*,°43,5 (39,0; 49,3)*18,5 (14,5; 22,0)*17,5 (11,0; 20,0)*18,0 (14,0; 20,0)*57,0 (52,8; 64,0)*57,5 (47,8; 63,3)*β4(60254,0 (47,8; 63,0)*;#o4β00,%2/((9)21952.7)2--β50/6-(AЧV+/PI–)-) ( >0,05).(-(Chlamydia trachomatis, STS,,22),-(49).1964.,,,,-.–,,. ., β015;[Lu J., 2012; Galimova E.F.
et al., 2015].. ., β016;,-,ё-.,.-,,,,Д. .,. ., β014; Sermondade N. et al., 2013],2013;.,,,ё ,cc.-ccacё-.197,,ё . .[., 2016; Kupka M.S., 2014].-,-,.,,. .[. .., 2017;. .2017;., 2016;. ., β016;. ., β016,., 2016].-,Д. ., β010Ж.ё,.,ё,,.,,,-ё-,-,.ё,,198-,-.718,78,,3040,-, γ8«»(570),-,-.,-. ., 2015 ;. ., β015; Schuppe,Дё,H.C., 2011; Jungwirth A.
et al., 2012; Agarwal A. et al., 2015].,),(-,(),-Д. ., β016; Redmon J. et al., 2013; Leushuis E., 2014].,-,-ё.ёc199-.,, β01β; Cooper T. et al., 2010; WHO, 2010],[ё( %),c,,aa,c.aaBloom oёo-o,.-,,–,Д. .ё-., 2006].,ё.ё-,.,,PI-[Tarozzi N. et al., 2007; Falzone N. et al., 2010].-AnV-FITC,ё,-.40PI,(Bloom21).200--21.()-; # ˂0,05, ## ˂0,001(0 )-(PI)* ˂0,05, ** ˂0,01,(),-(PI) –.-,.,,PIёLachaud ..,-.78,(PI+)-),PI ((p>0,05).-[Lachaud ., 2004],,Sion B.PI201.,-,,,(p<0,01)[Sion B., 2004]..
..,-:PI(«MШХОМЮХКr PrШЛОs»PI. ., β01β , β01β ].-14) [,,ё.in vitro (β4,1,5%γ%2ββ° ,-2)ё-.,,,,ё-.,,γ5% (γ5,6±γ,5%),γ4,8±γ,β%.,(PI+)202-β(40,6±1,0%β1,1±γ,0%).β4-in vitro( ˂0,05),(,21),,,-PI.,-( nV+/PI–)-()–-( nV+/PI+)-.in vitro4-2ёPI(-2,,. .21),.[. ., β01β , β01β ].β00–H2O2-,( nV+/PI+)-,-,PI.,,.,,-PI.-Bloomβ4--γ7°C,, . .203-ё-,-ё-.in vitro ( ,H2O2)PI( <0,05),-.«»(AnV–/PI–)-, (AnV+/PI–)-, (AnV+/PI+)-/(AnV–/PI+)-,.-–.,, (AnV–/PI+)[Glander H-J., 1999; Ricci G., 2002; Pena F.J., 2003;., β004].Sion B., 2004; Lachaud«»,/PI–)-, ( nV+/PI–)-: (AnV–( nV+/PI+)-2002; Shen H-M., 2002; MuratoriA,[Durn N.K., 2001; Schuffner A.,., β00γЖ.V,»PI («-),(AnV–/PI–)-ё(AnV–,/PI+)-–Vё.,( nV+/PI–)-,,( nV+/PI+)-.204,ё -,V,,:-– ( nV+/PI–)--() – ( nV+/PI+)-[Barroso G.
et al., 2000; Sion B. et al., 2004; ShenH-M. et al., 2002; Ricci G. et al., 2002]..Shen H-M.( nV+/PI+)-,,( nV+/PI+)-( nV+/PI–)-,,,,,[Shen H-M., 2002].,, β01β; WHO 2010][V.-β,5,:1,8,(17,8%– γ,7( ЧV+/PI–)10,1%),( ЧV+/PI+)-5,9%) ((β1,6%22).ёV-( ЧV+/PI–,)-( ЧV+/PI–)-( ЧV+/PI+)-(β0%-).,( ЧV+/PI–)(AnV+/PI+)-(r=0,7; <0,001),.205-,22.ё-() –(AnV+/PI–)γ(AnV–/PI–)(0,4γ( nV+/PI–)-,0,15), ( <0,001).( nV+/PI+)[Barroso G.
etal., 2000; Oosterhuis G.J. et al., 2000; Shen H-M. et al., 2002; Lachaud . et al.,2004],Ricci G.. [Ricci G., 2002].-,-,[Gandini L. et al.,2000; Shen H-M. et al., 2002; Riccioli A. et al., 2005].[Sun J.G. et al., 1997; Donnelly E.T.,et al., 2000; Gandini L. et al., 2000],( nV+/PI–)--206( nV+/PI+)-ДSion B.
et al., 2004; Glander H-J. et,al.,1999; Oosterhuis GJ. et al., 2000].,( nV+/PI+)-( nV+/PI–)-[Ricci G. et al., 2002].-,γ5%(AnV+)-,16%.(AnV+/PI–) ,β0%-,,«»,-TUNEL [Oosterhuis G.J. et al., 2000; Wang X. et al., 2003].ёFКs––FКsL.,ёFasFasL[Lee J. et-al., 1997; Print C.G. et al., 2000; Kierszenbaum A.L., 2001].FКsFКsL,,FКsёFКs-.(Fas+)-(AnV+)--,[Sakkas D. et al., 2002;McVicar CM. et al., 2004].FКs,207,Fas(85%, . .(5γ%, .
.41γ440),-78) ( <0,001). Fas.,,Fas(FКs+)-10%,-10%.FКs--.,Sakkas D.,(FКs+)-,[Sakkas D. et al.,1999a].(-,-,)-,(AnV+)FКs--.FКsLβ0%.-FasL-.,Riccioli A.[Riccioli A., 2005].FКsL,-,,,[Riccioli A. et al., 2005].FКsL,.,FasL,,208,,ё,γ0-FКsLё-sFКsL-–[Powell WC. et al., 1999].sFКsLRiccioli A.. [Riccioli A., 2005].–,-,,.FКsL,-FКsL.,,FКsL,FКs-,.,FКsL(Fas+)--,,-Fas,,(Fas+)--,.., FКsL,:.,,,,-209,,[Gandini L. et al., 2000;Shen H-M. et al., 2002].,,Fas–,()Fas-4-(CD95).FasL,CD95:ё-––FasL,Fas–[Paasch U.
et al., β004 ; Taylor S.L., 2004].,,,-Fas-,.Fas/FasL.,β4--in vitroγ7°Cё-.( nV+/PI–)(( nV+/PI+)-23).,V,(AnV+).,,,,210,(),ё().(Fas+)-23.β4--(0-γ7°C* ˂0,001)in vitroγ7°Cβ4–.,,-,γ7°C,,,-.,,,-ё,[Tarozzi N. et al., 2007; Seli E. et al., 2005],211ё,,(«»),[Sakkas D. et al., 1999 ,1999b, 2003; Tesarik J. et al., 2002; Shen H-M. et al., 2002].,,-ёAnV,,,Fas-,,-,ёin vitro,.Lachaud«.. [Lachaud»., β004Ж[Sakkas D. et al., 1999 ,–1999b, 2003].,,-,,,-.,,,PIin vitro (21),β4-,,,,,,4-.,,[Ricci G. et al., 2002].(-),[Tesarik J., 2002; Shen H-M. et al., 2002].212ё-,in,vitro.in vitro,β4--ICSI,,.,-,,,-:,-,1β-14,,()-,,(,)ёё-,-,.
.[., β015 ;. .-,-., 2015].,,,-.,,.-[. .., 1983].ё,213,.,,ё. .[ё., 1983].,ё,,, . ..-,,,.,-,.,.,,-ё..,,(«»),.-[Sakkas D. et al., 2003].ёё: 1-,–-ё; β-–214–; 3(24,25).24.( nV+/PI–)--25.(Fas+)--ё,215( nV+/PI–)-( ˂0,001),γ0%( ˂0,05),(Fas+)«»-,.,-ё.ё(7β-),,,.-,-..ceёa-.Д. ., β016;A.,-2017; Jungwirth A. et al., 2012; Leushuis E. et al., 2014].,,.,ё,216-,,.ё,–γ4β548,-..,: 1)-; β)77%-; 3)-,,.,(AnV+/PI+)--[Barroso G.
et al., 2000; Gandini L. et al., 2000; Oosterhuis GJ. et-al., 2000; Ricci G. et al., 2002].,,,.,,,,(Fas+)-Fas-,-.217,, ё(V+)-.ё()«»,. [Sakkas D., 1999 , 1999b].Sakkas D.eeaa-e.e,Д. ., β016Ж.,-,-,,(,,)74%-.,,.-( nV+/PI+)-,( ЧV+/PI–)-(r=0,β5; <0,05).218,,,,-., 2002].[Shen H-M.,FКs,,-.,ё,.,-,,-ё..-,-,,,.,.,,-,,,219.,-,.-,-,,-,-–.ё,,,,-,.Д. ., β015;. .. ., β014;., 2016],,--,.--.–(26).β0-,. .(r= –0,5; <0,01).22026.* ˂0,05(-)( ˂0,01)( nV+/PI–)-(27).,--.,.,,,-(ё) [Frohlich H., 1968Ж.,-221,Д. ., 1999Ж.( nV+/PI–) -27.-* ˂0,01(-,),«-»-,ё..«».-,ёД,.
.. .,., 1991;., 2012;. .. .., 2000;., 2013].-222.-,,, ,,.-ё(ё).–(-)..ёёёVё.[Blanc-Layrac G., 2000; Shen H-M., 2002; Martin G., 2005],-: ( nV+/PI–),( nV+/PI+)-,.V,,,ё,-,ё[Barroso G., 2000; Gadella B.M., 2002; De Vries K.J, β00γ;. ., 2010].223-:-ДDe Lamirande E. et al., 1997Ж,ДShen H-M. et al., 2002].,,-,-,. .[,ё-. ., β005Ж.(),Ca2+.,,,2+. .Д.
.., β016Ж.-,[-. ., β005Ж.,,().,.-,.224ё:Д-. ., β014;. .,. ., β016; Comninos A., 2014; Jung J.H. et al., 2014].2015;,.-,ё,. ., β015 ;[. ., β015Ж.-.,-,,(,,-).,-;-.,ё,,,,-,Д-. ., β016Ж.ё225-,c.c,ё,,:, Comet assay,TUNEL-SCSA.Д. .., 2015;. .,2016; Evenson D.P. et al., 2013; Muratori M. et al., 2008].ё;;;,-,,,,;ё,-ё, . ..,,,,«»V-FITC-ё-PI [Ricci G. et al., 2002].,( nV+/PI–)226(FКs+) --( >0,05).,γ1,6-,---.,,.,--20%,( nV+/PI–) -(--28).( nV+/PI-)-28.227β0%,,ё,.,,,.β0=7,1-–2P=0,1,-f=4β,194№(. 04.05.β016 .).262054β,β0,–,.( nV+/PI–) (-)()(1,1.( nV+/PI–)),228()( nV+/PI–)-(( nV+/PI–)-).(-β0%).,;,;-,ё–,.,-,,β0-,,,.229,-,.
.[.,2017].,,V.,( ˂0,001)-(AnV–/PI–)-,(AnV+/PI–)-,(29).ё29.* ˂0,001(),,,VДDurn N.K. et al., 2001;[Glander H-J. et al.,1999Ж,230,Schuffner A. et al., 2001].,:-,,-«swim-up»;,– 6-CFDA.PI,[Garner D.L. et al., 1986].-(AnV+/PI–),,,-/,( nV+/PI+)-.-(AnV–/PI–),(AnV–/PI+)-.,(AnV–/PI–),(AnV–/PI+)ё(AnV+/PI–)-,(AnV+/PI+)--.Sion B.. [Sion B., 2004],-.(AnV–/PI–)-ё(AnV–,/PI+)-(AnV–/PI–)-,.-,.,ё231(r=0,56;(AnV–/PI–)ё,<0,001)(AnV+/PI+)(AnV+/PI+)-(r= –0,5β; <0,001).,-,,,,-PI,, . ..ёVPI.,.ё,-,-,«.»,-,Д. .-., 2008; Lourenхo A.
et al.,β01γЖ.,ДPaasch U. et al., β004 Ж.-,(),.-–,,232-.,,,-10-..,,in vitro,,(AnV+/PI–)β-.60( ˂0,05)/,AnV,-,-4-(AnV+/PI–)( ˂0,001) (30).( nV+/PI–) -30.* ˂0,05, ** ˂0,001(233)-( >0,05).,.. [Paasch U., β004 ]Paasch U..,Paasch10U.∆Ψm,-9--γ.,ё,–β.-,,. ..,,(,-1β-β4 ),∆Ψm∆Ψm Д-. ., 2002,2003].,,,∆Ψm,-,-,,Д. .., β00γ;234. ..,,2008]..-. .[., 2016].-– Chlamydia trachomatis Д. ., β015;. ., β015;Chlamydia trachomatis –. ., β017].()-,Д.
., β006; Eley A. et al., 2005].Chlamydia trachomatis ()(AЧV+/PI–)-,(r= –0,9; <0,001).Chlamydia trachomatis (,E)–in vitro(-31).Eley A..,-,,:-[Eley A., 2005].,.,,,-Chlamydia trachomatis,.235-,,,in vitro,Chlamydia,trachomatis-.( nV+/PI–) -31.-6(1/ );* <0,0011–(56°C. trachomatis (3–1 );E) (0,12–/ ).(STS)1(STS)/,,-.Taylor S.L.10/ STSβ-,4-,-[Taylor S.L., 2004].Taylor-S.L.STS,,236.–,2–2-,[Aitken R. et al., 2010; Chen S.J. et al., 2013; Guerriero G.
etal., 2014].,,2in vitro,2-(AnV+/PI–)(,32).( nV+/PI–) -32.˂0,001; *(β-2222);#-(β5β00)β00237H2O2β-,AnV,,( nV+/PI–)-4,AnV-,, . .PI,ё-..,Taylor S.L., Donnelly E.T.β00,-H2O250% [Donnelly E.T. et al., 1999; Taylor S.L. et al., 2004].,β5H2O2,AnV--H2O2[Ramos L. et al., 2001].,H2O2.-,ё-,.,22,-.. .ё,,-,()-:(,-S-)238,-Д. ., β008 Ж.-ё.( >0,05).2,-2.,H2O2 [Hughes C.M. et al., 1996; Lopes S. et al., 1998].,,,-Д. .., 1999Ж.,,ДBejarano I. etal., 2014; Brody S., 2014].ёin–vitroα-,.,in vitroα-2-2-,.«600)»α-(40,60)239(300-ё,2.2-2β0022-(34).332-2-.,,-,,-[Hughes C.M.
et al., 1996; Lopes S. et al., 1998; Donnelly E.T. etal., 1999; Saki G., 2013].(AnV+/PI–) –33.γ00<0,0β; *1 – γ00+ β002 – 6005 – 600;22;γ(;β00240(+ β0023 – β00224–2;2.);2).-#-(AnV+/PI–) –34.-α– 40<0,0β; *1 – 40α+ β00α-;22;2 – 605 – 60γ(αβ00α(;2242;2.);#-2).2,23 – β00+ β00,-2,,.2β0022--,,ё(AЧV+/PI–)--.α(AЧV+/PI–),,,H2O2.241.-,-ё,,.,, . .-.-,-,ё-,.,,,,ё,ё-.,–()(35).-,(AnV+/PI–).1,,–.2421-35.(1 –; 2 – β060/;3–4mydia trachomatis; 5 – β(STS).β00;4–62)2; 6 –60,1/1Chla/,:-,.,. .,:,STS,«»2,-2.–FasLCD95.-,36.243ё -22in vitrot°ё;,-----36.,-,,,-,..244,.,,,,-,-,.,,,,-.-,--.,,-.--,-.Fas-(CD95)FКsL,,245-FКs-.,-in vitr,-CD95,( >0,05).,«,»(,FКs,-)ё–FКs.,,Д.., β014;. ., β016Ж.,,ёД. ., β01γ; Kashanian J., 2015].,,-,.,,,246.aё,oёeё ae ё,.,-,-,(–)-.–-–,,-,ё.,,ё.–,.:.:H2N-CH2-CH2-CH2-NH-CH2-CH2-CH2-CH2-NH-CH2-CH2-CH2-NH2(N,N’–(γ-) – 1,4);r = 202,3H2N-CH2-CH2-CH2-NH-CH2-CH2-CH2-CH2-NH2(N – (3-) – 1,4247);r = 145,2,,,.-,,,,-.,Д,.