贝那普利与氯沙坦对糖尿病大鼠的心肌保护作用

Cardioprotection of Benazepril and Losartan in Diabetic Rats

目的观察贝那普利与氯沙坦对糖尿病大鼠心肌细胞凋亡、纤维化的干预效果,探讨两者对糖尿病大鼠心肌保护的作用机制。方法将40只SD大鼠随机分为空白对照组(n=10)和糖尿病模型组(n=30),糖尿病模型组用链脲佐菌素(STZ)腹腔注射建模,成功后再随机分为糖尿病对照组(n=10)、贝那普利治疗组(n=10)和氯沙坦治疗组(n=10)。贝那普利治疗组给予贝那普利10 mg/(kg·d)灌胃,氯沙坦治疗组给予氯沙坦20 mg/(kg·d)灌胃,糖尿病对照组和空白对照组给予相同体积的生理盐水灌胃。给药9周后,观察各组心肌细胞凋亡、心肌组织Fas蛋白表达,Ⅰ型、Ⅲ型胶原含量,血清转化生长因子-β_1(TGF-β_1)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶组织抑制物-1(TIMP-1)蛋白表达的变化。结果与空白对照组比较,糖尿病对照组血管紧张素Ⅱ(AngⅡ)的含量明显增多(P<0.05),Fas蛋白表达率、凋亡指数明显升高(P<0.05),心肌细胞凋亡明显增多;Ⅰ、Ⅲ型胶原含量明显增多(P<0.05),存在间质纤维化,同时TGF-β_1、TIMP-1蛋白表达增多(P<0.05),MMP-1表达减少(P<0.05)。与糖尿病对照组比较,贝那普利治疗组和氯沙坦治疗组Ⅰ型、Ⅲ型胶原含量明显减少(P<0.05),TGF-β_1、TIMP-1蛋白表达减少(P<0.05),MMP-1表达增多(P<0.05);Fas蛋白表达率、凋亡指数明显降低(P<0.05),贝那普利治疗组AngⅡ的含量明显减低(P<0.05),氯沙坦治疗组AngⅡ的含量升高但差异无统计学意义。贝那普利治疗组与氯沙坦治疗组组间Fas蛋白表达率、凋亡指数及各项纤维化指标比较差异无统计学意义。结论糖尿病大鼠的心肌细胞凋亡明显增加,间质纤维化增加。贝那普利和氯沙坦均能抑制心肌细胞的凋亡和间质纤维化。

Objective To explore the possible mechanism of benazepril or Iosartan improving myocardial interstitial fibrosis and cardiomyocytes apoptosis in diabetic rats.Methods Forty Sprague- Dawley（SD） rats were randomly divided into 2 groups, 10 as normal control group and the other 30 as diabetic group which were induced by STZ, after the models were constructed successfully, randomly devided into diabetic conirol group, benazepril treated group, Iosartan treated group, each contains l O.Following the instruc tion,benazepril was administrated at the concentration of 10 mg/kg once a day,losartan was administated at the concentration of 20 mg/kg once a day,while in the diabetic control group and the normal control the same volume sodium chloride was administrated.After ten weeks, SP immunohistochemical staining was used to detect the level of Fas.Radioimmunity was used to measure the content of angiotensinⅡ （AngⅡ）.lmmunohistochemistry was used to measure the levels of type I collagen, type Ⅲ collagen, transforming growth factor （TGF）- β1, matrix metalloproteinase （MMP） 1, tissue inhibitors of metalloproteinases （TIMP）- 1 protein.Results compared to the normal control group,the content of Angll increased significantly,the rate of expression of Fas increased significant ly,the apoptosis index increased significantly the expressions of type I ,type Ⅲ collagen,TGF- β1 prptein,TIMP- 1 protein also in creased significantly, however,the expression of MMP- 1 protein decreased significantly.Compared to the diabetic control group, all the indexes were greatly improved in benazepril treated group.In Iosartan treated group, all the indexes except Ang Ⅱ were greatly im- proved.Conclusion Benazepril and Iosartan can improve obviously the myocardial inerstitial fibrosis,cadiocyte apoptosis in diabetic rats.