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1、氯沙坦及A779对糖尿病心肌病大鼠心肌间质纤维化的影响【摘要】目的观察氯沙坦对糖尿病心肌病大鼠心肌间质纤维化的影响并探讨其机制。方法将39只雄性Wistar大鼠给予链脲佐菌素(STZ)55?mg/kg一次性腹腔注射12周后,将血糖>16.7?mol/L且具有多饮、多食、多尿现象的36只大鼠纳入实验。实验大鼠随机分为糖尿病心肌病(DCM)组、氯沙坦组和A779+氯沙坦组,每组12只。给予氯沙坦组大鼠氯沙坦10?mg/(kg·d)灌胃,给予A779+氯沙坦组大鼠氯沙坦10?mg/(kg·d)灌胃和血管紧张素(17)受体拮抗剂A779100
2、?ng/(kg·d)尾静脉注射,给予DCM组大鼠等量生理盐水灌胃,治疗持续4周。第16周末采用心脏超声、Masson染色及RTPCR的方法测定大鼠的左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、短轴缩短率(FS)、左室射血分数(LVEF)、E/A(E峰/A峰)、左室心肌胶原含量、ACE2mRNA的表达。结果与DCM组比较,氯沙坦组和A779+氯沙坦组大鼠的LVIDs、LVIDd降低(P<0.01),E/A、FS、LVEF升高(P<0.01),左室胶原含量减轻(P<0.01),ACE2mRNA表达增高(P<0.01);与
3、氯沙坦组比较,A779+氯沙坦组大鼠LVIDs、LVIDd升高(P<0.05),E/A、FS、LVEF降低(P<0.05),左室胶原含量升高(P<0.05),ACE2mRNA表达无明显差异。结论氯沙坦通过Ang(17)途径减少纤维化及改善心功能。【关键词】氯沙坦;血管紧张素(17);血管紧张素转换酶2;A779;糖尿病;心肌病;大鼠,Wistar ToinvestigatetheeffectofLosartanandA779onmyocardialinterstitialfibrosisindiabeticcardiomyo
4、pathy(DCM).MethodsThirtyninemaleWistarratswereintraperitoneallyinjectedwithstreptozocin(STZ)toinducehyperglycemia.After12weeksoftheSTZinjection,ratswhosebloodglucosewashigherthan16.7?mmol/Landwhohadpolydipsia,hyperphagiaandpolyuriawererandomlydividedinto3groups:theDCMgro
5、up,theLosartangroupandtheA779+Losartangroup.TheDCMgroupwassubjectedtoperfusionofnormalsalineintothestomachoncedaily,theLosartangroupperfusionofLosartanoncedaily,andtheA779+LosartangroupperfusionofLosartanandinjectionofA779throughthetailveinoncedaily.Attheendoftheexperimen
6、t,LVIDs,LVIDd,E/A,LVEFandFSweredeterminedbyultrasound.ThenthecollagenlevelwasdeterminedbyMassonstaining,andthemRNAexpressionoftheangiotensinconversionenzyme2(ACE2)wasdeterminedbyrealtimeRTPCR.ResultsBytheendoftheexperiment,theLVIDs,LVIDdandthecollagenleveloftheLosartan
7、groupandtheA779+LosartangroupwerelowerthanthoseoftheDCMgroup(P<0.01),alsotheE/A,FS,LVEFlevelsandtheexpressionofACE2mRNAoftheLosartangroupandtheA779+Losartangroupwerehigherthanthoseof6theDCMgroup(P<0.01).TheLVIDs,LVIDdandcollagencontentoftheA779+Losartangroupwerehigherthan
8、thoseoftheLosartangroup(P<0.05),andE/A,FSandLVEFoftheA779+LosartangroupwerelowerthanthoseoftheLo