缬沙坦对阿霉素所致心肌损伤保护作用的相关机制研究

摘要

目的:探讨缬沙坦(Vat)对阿霉素(Dox)所致心肌损伤的保护作用及机制.方法:将24只Sprague-Dawley大鼠随机分4组:对照组(Con组)、Vat组(30mg/kg·d-1)、Dox组(15mg/kg)及Dox+Vat组,每组6只.6周后采用酶联免疫吸附试验(ELISA)法测定大鼠血清心肌肌钙蛋白Ⅰ(cTnI)和脑钠肽(BNP)水平、苏木精—伊红(HE)染色法观察心肌组织病理形态学改变,TUNEL法检测大鼠心肌细胞凋亡率,Western bloting法分析血管紧张素Ⅱ1型(AT1R)、2型受体(AT2R)和凋亡相关蛋白Bax、Bcl-2蛋白表达量.结果:与Con组大鼠比较,Dox组大鼠血清cTnI和BNP含量、AT1R表达量、心肌细胞凋亡率及Bax/Bcl-2比值均明显升高(P<0.05),心肌纤维排列紊乱;而Dox+Vat组大鼠血清cTnI和BNP含量、AT1R表达量、心肌细胞凋亡率及Bax/Bcl-2比值均较Dox组明显降低(P<0.05),AT2R表达升高(P<0.05),心肌病理结构损害得到明显改善.结论:Vat对Dox所致的大鼠心肌损伤具有保护作用,其机制可能通过上调AT2R的表达,提高Bax/Bcl-2比值,从而抑制细胞凋亡有关.%Objective:To investigate the protective effect and mechanism of valsartan(Vat) on myocardial injury induced by doxorubicin(Dox).Methods:Twenty-four Sprague-Dawley rats were randomly divided into 4groups(n=6 per group):control group,Vat group,Dox group(15mg/kg) ,Dox+Vat group(30mg/ kg).After 6 weeks,cTnI and BNP levels were measured by ELISA.Pathological changes of myocardial tissues were observed by hematoxylin-eosin (HE) staining,and apoptotic rate of cardiomyocytes was detected by TUNEL.The expression of AT1Rand AT2Rand Bax/Bcl-2 ratio were analyzed by western blotting.Results:Compared with the control group,the levels of cTnI and BNP in serum,cell apoptotic rate,AT1Rexpression level and Bax/Bcl-2 ratio were increased in the Dox group(P<0.05) , and myocardial fiber arrangement was disordered.The effects of Dox were reversed in the presence of Vat, and the AT2 Rexpression level was significantly elevated in Dox+Vat group(P<0.05).Conclusion:Vat could protect rats against Dox-induced myocardial injury by the up-regulation of AT2Rexpression and the inhibition of cell apoptosis.