血管紧张素Ⅱ受体拮抗剂对心肌重构的保护机制.pdf

临床心血管病杂志2005年11月第21卷第11期·663·

血管紧张素Ⅱ受体拮抗剂对心肌重构的保护机制

杨永健张鑫孙梅芹

[摘要]目的：探讨血管紧张素I(AngII)受体(AT，AT)拮抗剂对梗死心肌组织中钙蛋白酶(calpain)系
统的作用。方法：结扎大鼠左冠状动脉建立心肌梗死(MI)模型，将成功造模的96只大鼠分为4组，每组24只。
各组术后1、3、7、14d分别检测左心室游离壁(【VFw)、室间隔(IS)、右室壁(RV)的calpainI、Ⅱ及钙蛋白酶抑制
蛋白(calpastatin)表达。结果：术后14d，手术组Is的calpainI蛋白表达与LVFw的calpainII蛋白表达均明显
高于假手术组、手术加缬沙坦组及手术加PD123319组(均P<20．01)；各组LVFw、RV的calpainI蛋白表达，Is、
RV的calpainlI蛋白表达以及Is、LVFw、RV的calpastati~蛋白表达差异均无统计学意义。结论：calpainI参与
MI的晚期重塑，calpainⅡ参与早期缺血心肌组织的损伤作用。MI病理过程中，calpainI和Ⅱ的上调通过AT
起作用，AT受体拈抗剂的心脏保护作用与其抑制了calpain系统有关。
[关键词]心肌梗死；受体，血管紧张素II；钙蛋白酶；心肌重构
[中图分类号]R540．4[文献标志码]A[文章编号]1001—1439(2005)11-066303

AstudyonprotectivemechanismofangiotensionⅡreceptor
antagonistsintheratmyocardialremodeling

YANGYongJianZHANGXinSUNMeiqin
(DepartmentofCardiology，GeneralHospitalofChengduArmy，Chengdu，610083，China)

AbstractObjective：ToinvestigatetherolesofangiotensionII(AngⅡ)receptors(AT1，AT2)antagonistson

ealpainsystemininfarctedmyoeardiuminrats．Method：Ratmyoeardiuminfarction(MI)modelwasestablishedby

permanentligationoftheleftcoronaryartery．ThetreatmentoftheAT1receptorantagonistvalsartan(10mg。

kg一·d一)orAT2receptorantagonistPD123319(30mg·kg一·d一)wasstarted7dayspriortosurgery．On

day1，3，7and14afterMI，proteinlevelsofI，IIandealpastatinweredeterminedinleftventrieularfreewall

(LFW)，interventrieularseptum(IS)andrightventricular(RV)．Result：CalpainIproteinlevelswereincreased

inIS14dayspostMI，whereastheproteinlevelsofcalpainI1weremaximallyincreasedinIVFW3dayspost

MI．valsartandecreasedproteinup—regulationofcalpianIandII，andreducedinfarctsizeandinterstitialfibro—

sis．PD123319didnotaffectcalpainIorIIup—regulationintheinfarctedmyoeardium，butdecreaseinterstitial

fibrosis．CalpastatinproteinexpressionwerenotaffectedbyATreceptorsangagonists．Conclusion．CalpainIis

involvedincardiacremodelinginthelateandcalpainIIcontributingtocardiactissuedamageintheearlyphaseof

MI．Theup-regulationofcalpainIandIIispartlymediatedviatheAT1receptorandcanbereducedbyAT,re—

eeptorantagonists．

KeywordsMyo