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1、氯沙坦對阿霉素腎病大鼠腎臟保護(hù)作用探究【摘要】目的探討氯沙坦對阿霉素腎病腎臟的保護(hù)作用及機(jī)制。方法48只Wistar大鼠隨機(jī)分為對照組、腎衰組、氯沙坦組,每組16只。腎衰組及氯沙坦組大鼠腹腔注射阿霉素4mg/kg,每周1次,持續(xù)5w,制作阿霉素腎病大鼠模型;對照組應(yīng)用同樣的方法注射生理鹽水。模型復(fù)制成功后,氯沙坦組大鼠給予氯沙坦1.2mg/只灌胃,1次/d;腎衰組給予同等量生理鹽水灌W,1次/d,均連續(xù)給藥2w。生化法檢測24h血尿素氮(BUN)、血肌肝(Cr),化學(xué)比色法檢測腎皮質(zhì)中丙二醛(MDA)、超氧化物
2、歧化酶(SOD),RTPCR方法檢測腎組織ATI、AT2、ACE及AGTmRNA表達(dá)。結(jié)果與對照組比較,腎衰組血清BUN、Cr均顯著升高,腎皮質(zhì)中MDA升高,SOD降低(P<;O.05);氯沙坦組與腎衰組比較,血清BUN、Cr均顯著降低,腎皮質(zhì)中MDA降低,SOD升高(P<;O.05)o與對照組比較,腎衰組腎臟ATI表達(dá)上調(diào),AT2降低,AGT和ACE水平增高(P<;O.05);氯沙坦組轉(zhuǎn)為ATI下調(diào),AT2表達(dá)接近對照組水平,AGT水平降低,ACE水平降低但仍高于對照組水平(P<;O.05)o
3、結(jié)論氯沙坦具有延緩阿霉素腎病大鼠腎功能不全進(jìn)展,減少氧化應(yīng)激損傷的保護(hù)作用?!娟P(guān)鍵詞】氯沙坦;阿霉素;腎素血管緊張素系統(tǒng)(RAS);腎功能【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