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1、氯沙坦对阿霉素肾病大鼠肾脏保护作用探究【摘要】目的探讨氯沙坦对阿霉素肾病肾脏的保护作用及机制。方法48只Wistar大鼠随机分为对照组、肾衰组、氯沙坦组，每组16只。肾衰组及氯沙坦组大鼠腹腔注射阿霉素4mg/kg,每周1次，持续5w,制作阿霉素肾病大鼠模型；对照组应用同样的方法注射生理盐水。模型复制成功后，氯沙坦组大鼠给予氯沙坦1.2mg/只灌胃，1次/d；肾衰组给予同等量生理盐水灌W,1次/d,均连续给药2w。生化法检测24h血尿素氮(BUN)、血肌肝(Cr),化学比色法检测肾皮质中丙二醛(MDA)、超氧化物
2、歧化酶(SOD),RTPCR方法检测肾组织ATI、AT2、ACE及AGTmRNA表达。结果与对照组比较，肾衰组血清BUN、Cr均显著升高，肾皮质中MDA升高，SOD降低(P<；O.05)；氯沙坦组与肾衰组比较，血清BUN、Cr均显著降低，肾皮质中MDA降低，SOD升高(P<；O.05)o与对照组比较，肾衰组肾脏ATI表达上调，AT2降低，AGT和ACE水平增高(P<；O.05)；氯沙坦组转为ATI下调，AT2表达接近对照组水平，AGT水平降低，ACE水平降低但仍高于对照组水平(P<；O.05)o
3、结论氯沙坦具有延缓阿霉素肾病大鼠肾功能不全进展，减少氧化应激损伤的保护作用。【关键词】氯沙坦；阿霉素；肾素血管紧张素系统(RAS)；肾功能【Abstract】ObjectiveToinvestigatetheprotectingeffectofLosartanonthekidneyoftheratswithuninephrectomizedadriamycininducednephrosisandstudyitspossiblemechanisms.MethodsExperimentalnephriticsyn
4、dromemodelwasinducedwithrepeatedperitonealinjectionsofadriamycin.Ratswererandomlydividedintocontrol,model(ADR),losartan(ADR+ARB)groups,respectively.Theanimalmodelswereinjectedadriamycin(5mg/kg)throughtheabdominalcavityfor5w,thecontrolgroupwereinjectedphysiol
5、ogicalsalineasthesamemethod.Theindexesofoxidativestressreactionoftherenalcortex,malondialdehyde(MDA),superoxidedismutase(SOD)weremeasuredbychemicalchromatometry.ThekidneyATI,AT2,ACEandAGTmRNAexpressionswereassayedbyRTPCR.ResultsComparedwiththoseofcontrolgrou
6、p,thelevelsofbloodurinenitrogen(BUN)andserumcreatinine(Cr),MDAwereincreased,thelevelofSODwasdecreasedinADRgroup・ComparedwiththoseofADRgroup,thelevelsofBUN,CrandMDAweredecreased.ThelevelofSODwasincreasedinADR+ARBgroup.TheATI,ACEandAGTmRNAexpressionsinADRgroup
7、werehigherthanthoseofcontrolgroup・TheAT2mRNAexpressionwaslowerthanthatofcontrolgroup・TheATImRNAexpressioninADR+ARBgroupwaslowerthanthatofADRgroup,whiletheAT2mRNAexpressioninADR+ARBgroupwassimilartothatincontrolgroup.TheAGTandACEmRNAexpressionsinADR+ARBgroupw
8、erelowerthanthoseofADRgroup,whileACEmRNAexpressionwashigherthanthatofControlgroup.ConclusionsLosartonhasprotectiveeffectsagainstrenalinjuriesinducedbyADR・[Keywords】Losartan；Adriamycin；Reninangio
