他汀类降脂药在急性冠脉综合征中的应用

他汀类降脂药在急性冠脉综合征中的应用 1v??s??,???0??.???????D???.???????R???e????[J]1.?1?? ?G???]??,1999,20(2):52 2v???????,??????,??????,?>.?b?????s???????s?U?t?????????S?? ?U????ROS17/12.8?????]?4?T?????:???e[J].?T???t???4???R?] ???t??????,2000,16(3):400 3v?KarinM.Signaltransductionfromthecellsurfacetothenucleusthroughthe phosphorylationoftranscriptionalfactors[J].CurrOpinCellBiol,1994,6: 415 4v?MiyataT,InagiR,IidaY,etal.Involvementof.?2-microglobulinmodi2 fiedwithadvanced,ghycationendproductsinthepathogenesisofhemodialy2 sis-associatedamyloidosis:inductionofhumanmonocytechemotaxisand macrophasesecretionoftumormecrosisfacror-.?andinterleukin-L[J]. JclinInvesb,1994,93:521 5v?LidaY,MiyataT,InagiR,etal..?2-Microglobulinmodifiedwithad2 vancedghycationendproductsinducesinter-leukin-6fromhuman macrophages:roleinthepathogenesisofhemodialysis-associatedamyloido2 sis[J]1BiochemBiophysRescommun,1994,201:1235 6v???????,?a????,?Z?i,?>.?T?????t?????S???U????UMR106?????] ?4??????[J]1,2000,16(3):400 7v?ClossEI,MurrayAB,SchmidtJ,etal.c-fosexpressionprecedesosteoger2 risdifferentiationofcartilagecellsinvitro[J].JCellBiol,1990,111(3): 1313 8v?MccabeLR,KochxM,lianJ,etal.Selectiveexpressionoffosandjun- relatedgenesduringosteoblastproliferationanddifferentiation[J].ExpCell Res,1995,218:255 9v???????,????.?????????????????e?????u?T?????e[J],?T?????e?? ???W??,2000,6(2)83-86 10v???????,?<????,?1?W??,?>.???e???????6???e?S????????????c -fos?????T?????e[J]1,2000,6(3):9 11v?MunchG,ThomeJ,FoleyP,etal.Advancedglycationendproductsin ageingandAlzheimersrsdisease[J].BrainResRev,1997,23:134 12v?KassemM,OkazakiR,HarrisSAetal.Estrogeneffectsoninsulinlike growthfactorgeneexpressioninahumanosteoblasticcelllinewithhighlev2 elsofestrogenreceptor[J].CalcifTissueInt,1998,62(1):60 13v?KurlandES,RosenCJ,CosmanF,etal.Insulin-likegrowthfactor-Iin menwithidiopathicosteoporosis[J].JClinEndocrinolMetab,1997,82: 2799 14v???????,?????z,?????n.?????s?U?t???????.???????R??[J]1, 2000,20(1):17 15v??a????,????,???K??.2?????H?????J?D?JGH,IGF-L?????A???? ???????s???6??[J]1,2000,8(2):81 16v?DungorDB,CheethamTD.Growthhormoneinsulin-likegrowthfactorI axisininsulin-dependentdiabetesmellitus[J].HormRes,1996,46:2 17v?EriksenEF,lamgdahIBL.Thepathogenesisofosteoporosis[J].Hormone Research,1997,48(Supple.5):78 18v?JehlePM,TehleDR,MohanS,etal.Serumlevelsofinsulin-likegrowth factorsystemcomponentsandrelationshiptobonemetabolismintypeIand typeIIdiabetesmellituspatients[J].JEndocrinol,1998,159:297 19v??/?j,???W??.???e?????R?????s?U?t??????[J]1, 2000,20(1):21 20v?HaydenJM,MohanS,BaylinkDJ.Theinsulin-likegrowthfactorsystem andthecouplingofformationtoresorption[J]1Bone,1995,17(2Suppl):93 21v?OkazakiR.Glucocorticoidregulationofinsulin-likegrowthfacfor-bind2 ingproteinexpressioninnormalhumanosteoblast-likecells[J].En2 docrinology,1994,134:126 [?L?H???t:2003-08-28] ???D?????,???e?f?h???0???2???T?????e ???7?j,??????,??????,?????l (?????G?????>?8?????d?%???G????????,???Kv?????v?056002) [???I??]v?v????0???2??;???,;???? v?v??e???????b?????(???0???)???O?>??5???h???d?x???? ?????K?h???S???D?t??????(4S)v1?????F???????????b?6?? (WOSCOPS)v1???????????5???6??(CARE)v1???S???D???????? ?????t????(LIPID)???????????e???????????0???U???4???b ????(AFCAPS/TexCAPS)????????,???????????????x??,???z ????????????????,???????????????????????G?????? [1??4] v, ???Y?????6???S???????.,?e???.??????sM?,?e????sgv,?????? ?;???4??,???D???.?,?????Y???????????T?????y????,?o?? ?Y?e?f?h???0???2??(ACS)?T?????e?6?????Y?????y??v, v????D???????????,???e ?D?8???D???????j???h???????????z?V?js6?????? ????,???n?S???Dv1???S???Dv1?t?S???Dv1???S???Dv1?H???S???D ?>,???4???5???j:3????3?b???(????????A??????(HMG- COA??????)???L?Wv,HMG-COA???????Y???????2?S???u?T ?????I?h???t??,?:???D?????,?????Y?????h???L???????? ?e,?????????????2?S???7,?D?T????????,???????O???????, ??????????(LDL-C)??????????????,???:???????T?0???i?? LDL-C???????????????O?RLDL-C???????2?:???J??v,?? ?4,???D???????????????L???,????B-100?e???????2?S,?? ?:???7???????C?a???0???,????(TRL)???2?S???]??v,?G???? ?????D?????,?????0???<??LDL-C???T?<?VHDL-C(?????? ?,??????????)???e,???a???0??(TG)???e???j???r?RTG???? ?x??????LDL?j??????v, v?S???t?????]?t?]?????D 153?T???G?2?W??v?2004?????( ?? 1 statin-C 2AC ACS???t?????]???? ?Dsg?????????????x??????????v,?e?????????T,?0?o?y???I ???s:o??????x?????z?7?h;o????b?????S?]???D?8???hv,?? ?????0???U???????]?j?0????:?4?W?????Pv1?,?Ev1??????v,?8 ?????????????Y?????????P?????C???????????h???,?Ev,?? ?????e???????????J???D?Z?H?L?????????????t?G?h????,?D ??????v1????v1?????h?sv1???????????L?p???4v1???????0???n ?>,???i???t???????x??,?????D???R?x???4?????????????? ????????,?Y???????K?5?W?:?0????????,?????D?O??v1???? ??v1???????????????h?????????????t????,?s?S?D?;???j?? ?h????,???????tACSv, 3v????D?????,???eACS?T???e???]?????D ?h?????;???????%???z?j,?D?J???????x???R?????????? ?????????????E???9v,???D?????,?????Y?i??????LDL-C?x ??,???7?,?E??????????,???7?????,?e?C??,?????????C??, ?????????????:???????U???????O,?D???????hv,?x???????T ????,?????????????R,???????Y?????????y,?Z?Y???D?????? ?????t?????R?z??????,???????4???????Y?????w?????? ?? [5,6,12] v,???4,???D?????,???i???e???)?.?,???e???4???? ???0???U???4???e:o????????A??????????????,???????R?? ?D????????????????????NO???2?S?<???0??;o????????A?? ???0???U???????????????S,???D?????????D?????????????? ???????????????i???t???L???e;o????7?D?8???S?????????0 ???U?????[?????h????v,?-??ACS???t??,???????E???L?? ?? [7] ,???????????D?????,?????.?,?4???e???????Y?Y?1???D ?????????e??ACS???J???]?????D [14,15] v, 4v????D?????,?????e??ACS???????x?????? ?????0?????????b???T???,???????h???d?x???????D?0 ?????????V?j?f?h?????????R3??6?y?2?????Jv,?????????? ???i?x???6??,???????V?Y?1?eACS?????????,???????????? ???????[ [8??11] v,?????Y???????D???????????T???]????1995 ??1998???T58?y?????????????H?L???????0???hAMI???J?? ?????????????????t???e???D?????,????????????,?????? ?R,?????t???5?e?????D???????J???????????????y?5?e?J?? ??25%v,???RAMI???t???e???D?????????R?z?A?????Rv,?? ???0?????e???S???DACS???t???J?????b?????x??????:?? LAMIT(1999)\PAIS(1997)\L-CAD(1998)\PTT(1999)PECIFE(1999)?>(????1),?V ???????j:ACS???J???t?5?e???D ???????????A?????????x??????,???????????????????t???? ??????,?:????????,ACS???t???e???D???????0?????????? ?hv,?7?????D?????x???????J?????????h?????x???? ?? [14??16] ,?V???????t???e???D??????????,?????R?z?????? ??v1?w??????,?z???A???D??????????v,?????j?eACS???t?? ?e???D?????????????j?0????????v,?Z?????6???U?B???V?? ?O,?6?0???i???D???hv,???????0???????h???d???x???????? ?e?????T,??T(???S???D?????f?h???0???2??????)v1 Z(?????????????R???S???D??S???????6??)v1ROVIT (???S???D?4?H???S???D?e?????????????T???????6??),???? ?6???????]?????????????????:?y????????:o?ACS???t???e ???D???Y?m???0?K?D???????z???<??;o?ACS???J?5?e???D?? ?????????????j???2?,?W??;o??D?,?x???5?:??ACS???J,?? ?D???????e?9???R?O?>;o??D?,?????L?v?????x??;o????D?? ??????ACS?b?????e???j?L?R?D?,?x???)????????v,?????v ?R????????v, ??1v????D???e??ACS???t???J???O???d?x?????? ?6??????(????)?????5 ?????? n???? LAMIT(1997)3d69v?v??????????????S?????? PAIS(1997)48h10v?v????t?e???8???6???? LCAD(1998)6d126 ?A?????tACS?x??????,2???R?5 ?????R?????????????????]?C?j 17%?R34%(P<0103) PTT(1999)6h(AMI)164 ?A???x?????R,????6?y?2?R???? ???????? PECIFE(1999)10d60v?v??A??????????,???D?????s v?v???:LAMIT:?????????????f?h?????????R???D?,?R?,?????????? (Lipid-AMILoweringStudy);PAIS:?????????f?h?j?D?h???2???????? ?g??????(Pravastatininacuteischemicsyndromes);L-CAD:?f?h???0???? ?R???,?????????t?R???t?<??(LipitsinCoronaryarterydisease);PTT:?? ?????R???8?W??AMI??????,???????t?w??????(ProvastatinTurkishtri2 al);PACIFE:???????????????j?D?R??????????????(Reductionofcholes2 terolinischemiaandfunctionoftheendothelium) 5v????????D???????eACS???????e???r ???L?i???O???d?6???V?Y?1?eACS???t???e???D??????, ?Z???0?????????????K??????????Duke?h??Durham?G???T?? Duke?x???6???D??L.KristinNewby?????G?1???6??,?]?????o ?????j?x?????????x???%??,???????Y?eACS???J?T,???t?? ?e???D???????????????????????J???0?x???O?>,?Z???????? ?x???5???????J???0?????? [13] v,????,?7?????????d??ACS ?4???0???????Y?L?????????J,???e?????R?????424h?????? ?D?,????,?????????j?????????.?Fv,???????J??LDL-C?x ???h???4?>??314mmol/l,?????t???-?????????D?????,????v, ??LDL-C?j216??314mmol/l,?Y?m???e?r?-?x???o??v,???0 ???J???j,???????J?????????:????,LDL-C>216mmol/l?r?? ???????????,????v,????ACS???J,?P?????e?.?,????,?o?? ?Y???D??????,?5?????????f?h?t?????????A???????j?D?? ??,?????0?i?????[:o?v1???t?????????i;o?v1???t?e???????? ???J???t?5?????????h;o?v1???7???,??????????,?????i???? ?????v?????????,????v,?????x???(???e???D???????????? ???????????????????W??,???4?????x?????????e???W???V?? ?h,?i?e40??80mgv,?7?????t???e???W?????O,?j10mg?????? ?dv,???????????h???x??????,?7?????D?????x???8???????? ?e20mg???????d [14] v,???D?????????f?????????e?Y?y?????? ??,?x???(?7??,?Z???????t,?R???f??,???????Y???b?????t ????v,???????e?R?W??????,?\???e?T?5?????????h?W??v,?R ???????????2???e???????O,?o???R?g?????????5???????2?? ?ev,?e???t?????O???????J?0??????,???t??????????,?0?? 253?T???G?2?W??v?2004?????( ?? PACAto ACPE- 1v?SacksFM.Lipid-lowingtherapyinacutecoronarysyndromes[J].JAMA, 2001,285:1758-1760 2v?LibbyP.Currentconceptsofthepathogenesisoftheacutecoronarysyndromes [J].Circulation,2001,104:365-372 3v?PedersonJR,OlssonAG,FaergemanV,etal.Lipoproteinchangesandre2 ductionintheincidenceofmajorcoronaryheartdiseaseeventsintheScandi2 navianSimvastatinSurvivalStudy(4S)[J].Circulation,1998,97:1453- 1460 4v?FlakerGC,WarnicaJW,SacksFM,etal.FortheCholesterolandRecurrent Event(CARE)investigators.Pravastatinpreventsclinicaleventsinrevascu2 larizedpatientswithaveragecholesterolconcentrations[J].JAmCollCardi2 ol,1999,34:106-112 5v?DupuisJ,TardifJC,CernacekP,etal.cholesterolreducationrapidlyim2 provesendothelialfunctionafteracutecoronarysyndromes.TheRECIFEtrial [J].Circulation,1999,99:3227-3233 6v?KayikcitatinM,TurkogluC,CanL,etal.Thecombineduseofpravastatin andangiographicalresults[J].JAmCollCardiol,2000,35:345A-346A 7v??????f,???w?f,?????v,?>1[M]1: ???7???G???<?z,2003,1:311-321 8v?WilliamsJK,SukhovaGK,HerringtonDM,etal.Pravastatinhascholes2 terol-loweringindependenteffectsonthearterywallofatheroscleroticmon2 keys[J].JAmCollCardiol,1998,31:684-691 9v?KroneW,MullerWD.Lipid-loweringtherapyandstabilizationof atheroscleroticplaques[J].ThrombHaemost,1999,82(Suppl1):60-65 10v?CrisbyM,NordinFG,ShahPK,etal.Pravastatintreamentincreasescol2 lagencontentanddecreaselipidcontent,inflammation,metalloproteinases, andcelldeathinhumancarotilplaques:implicationsforplaquestabilization [J].Circulation,2001,103:926-933 11v?CortiR,FayadZA,FusterV,etal.Effectsoflipid-loweringbysimvas2 tatinonhumanahteroscleroticlesions[J].Circulation,2001,104:249-252 12v?RauchU,OsendeJI,ChesebroJH,etal.Statinandcardiovasculardis2 eases:themultipleeffectsoflipid-loweringtherapybystatins[J]. Atherosclerosis,2000,153:181-189 13v?L.KristinNewby.Earlystatintreatmenthasbenefitonacutecoronarysyn2 dromesonlyinpatientswithhyperlipidemia[J].JAMA,2002,287:3087- 3095 14v????w?f,???h??,?????f,?>1[ J]1,2002,11:651-654 15v?????,???x??,??????,?>1C D40Lv1??????????-9??C??????????????[J]1, 2003,3:165-168 16v?????,?a??,????,?>1[ J]1,2003,4:219-220 [?L?H???t:2004-02-10] ?m?s???????????,?6?????? ???? 1 (????),???R1 ,?a???72 (???d) (11,????v?????v?210000;21) [???I??]v?v??m?s????;????;?i?1?h v?v???1994???m?s(Leptin)?????????????????? 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