氯沙坦对阿霉素肾病大鼠肾脏保护作用的研究

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1、氯沙坦对阿霉素肾病大鼠肾脏保护作用的研究【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8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mg/kg，每周1次，持续w，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/只灌胃，1次/d;肾衰组给予同等量生理盐水灌胃，1次/d，均连续给药w。生化法检测2h血尿素氮(BUN)、血肌酐(Cr)，化学比色法检测肾皮质中丙二醛(MDA)、超氧化物歧化酶(SOD)，RTPCR方法检测肾组织AT1、AT2、ACE及AGTmRN

2、A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【关键词】氯沙坦;阿霉素;肾素血管紧张素系统(RAS);肾功能【Abstract】ObjectiveToinvestigatetheprotectingeffectofLosartanonthekidneyoftheratswithuninephrectomizedadriamycininducednephrosisandstudyitspossiblemechanisms.MethodsExperimentalnephriticsyndromemodelwasinduced

3、withrepeatedperitonealinjectionsofadriamycin.Ratswererandomlydividedintocontrol,model(ADR),losartan(ADR+ARB)groups，respectively.Theanimalmodelswereinjectedadriamycin(mg/kg)throughtheabdominalcavityforw,thecontrolgroupwereinjectedphysiologicalsalineasthesamemethod.Theindexesofoxidativestre

4、ssreactionoftherenalcortex,malondialdehyde(MDA),superoxidedismutase(SOD)weremeasuredbychemicalchromatometry.ThekidneyAT1,AT2,ACEandAGTmRNAexpressionswereassayedbyRTPCR.ResultsComparedwiththoseofcontrolgroup,thelevelsofbloodurinenitrogen(BUN)andserumcreatinine(Cr),MDAwereincreased,theleve

5、lofSODwasdecreasedinADRgroup.ComparedwiththoseofADRgroup,thelevelsofBUN,CrandMDAweredecreased.ThelevelofSODwasincreasedinADR+ARBgroup.TheAT1，ACEandAGTmRNAexpressionsinADRgroupwerehigherthanthoseofcontrolgroup.TheATmRNAexpressionwaslowerthanthatofcontrolgroup.TheAT1mRNAexpressioninADR+ARBg

6、roupwaslowerthanthatofADRgroup,whiletheATmRNAexpressioninADR+ARBgroupwassimilartothatincontrolgroup.TheAGTandACEmRNAexpressionsinADR+ARBgroupwerelowerthanthoseofADRgroup，whileACEmRNAexpressionwashigherthanthatofControlgroup.ConclusionsLosartonhasprotectiveeffectsagainstrenalinjuriesinduce

7、dbyADR.【Keywords】Losartan;Adriamycin;Reninangiotensinsystem(RAS);Renalfunction血管紧张素Ⅱ型受体拮抗剂(AngiotensinⅡtypeⅠreceptorantagonist，AT1RA)具有降压效果，能够延缓肾脏疾病动物模型肾脏损伤进展，应用于临床延缓肾功能不全进展的治疗中〔1,2〕。氯沙坦(Losartan，ARB)是临床用于延缓肾功能不全进展的血管紧张素Ⅱ型受体拮抗剂，具有良好的疗效，但其对肾脏保护作用的具体机制尚不完全清楚。阿霉素肾病大鼠肾