缬沙坦及氟伐他汀对糖尿病大鼠肾脏保护作用及对icam-1表达影响

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1、缬沙坦及氟伐他汀对糖尿病大鼠肾脏保护作用及对ICAM-1表达影响[摘要]目的从影响细胞间黏附分子-1（ICAM-1）表达的角度，探讨血管紧张素Ⅱ受体拮抗剂缬沙坦和羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂氟伐他汀对糖尿病大鼠肾脏病变的保护作用及其可能机制。方法通过链脲佐菌素诱导建立糖尿病大鼠模型并进行分组，检测肾重、肾脏肥大指数、血糖、血脂、血肌酐、尿素氮、24h尿蛋白定量，应用免疫组织化学法和逆转录聚合酶链反应（RT-PCR）分别从蛋白及mRNA水平检测肾组织ICAM-1的表达，光镜及电镜下观察肾组织病理学改变，并应用计算机图像分析系统进行定量分析。结果单

2、药及两药联用组肾脏肥大指数、24h尿蛋白定量、血脂、血肌酐、尿素氮、肾组织ICAM-1表达均与糖尿病模型组有明显差异（P＜0.05或P＜0.01）。各治疗组肾脏病理改变有不同程度的减轻，以两药合用组减轻最明显。结论ICAM-1参与了糖尿病肾病的发生和发展，氟伐他汀和缬沙坦均可降低糖尿病大鼠肾脏ICAM-1的表达，且两药联用对糖尿病大鼠肾脏具有协同保护作用。�[关键词]糖尿病肾病；缬沙坦；氟伐他汀；细胞间黏附分子-1；大鼠�[中图分类号]R587.2；R-33[文献标识码]A11[文章编号]1671-7562（2007）02-0095-05��Protectivee

3、ffectsofvalsartanandfluvastatinonthekidneysofdiabeticratsandexpressionofICAM-1��XUEJia,SHIHui2(1.DepartmentofGeriatrics,DrumTowerHospitalofNanjing,Nanjing210008,China;2.Department�ofNephrology,theAffiliatedHospitalofNantongUniversity,Nantong226001,China)��Abstract:ObjectiveToinvestiga

4、tetheprotectiveeffectsofangiotensionⅡreceptorantagonistvalsartanandhydroxymethyl-glutarylcoenzymeA(HMG-CoA）reductaseinhibitorfluvastatinonthekidneysofdiabeticrats,andstudytheirpossiblemechanismsrelatedtointercelluaradhesionmolecule-1(ICAM-1）expression.MethodsRatsweredividedintothenorm

5、alcontrolrats（groupNC),streptozotocin-induceddiabeticrats（groupDM),diabeticratstreatedwithvalsartan（groupDV),diabeticratstreatedwithfluvastatin（groupDF）anddiabeticratstreatedwithvalsartanandfluvastatin（groupDVF).IntrarenalICAM-1contentand11mRNAexpressionweremeasuredbyimmunohistochemic

6、altechniqueandreversetranscriptas-polymerasechainreaction(RT-PCR）techniquerespectively.Pathologicalchangesofrenaltissuewereobservedthroughlightmicroscopyandelectronmicroscopy.ResultsThereweresignificantdifferencesinkidneyhypertropathyindex,24-hoururinaryprotein,lipid,bloodureanitrogen

7、(BUN),serumcreatinine(Scr)andexpressionofICAM-1betweentreateddiabeticratsanduntreateddiabeticrats(P＜0.05orP＜0.01).PathologicalchangesonkidneyweremuchlighterintreatedgroupthanthatingroupDM.ConclusionGlomerularICAM-1expressionmayincreaseindiabeticnephropathy,whichcontributingtotheoccura

8、ncean