替米沙坦对糖尿病心肌病大鼠心肌超微结构的影响及其作用机制  

Effect of telmisartan on myocardial ultrastructure in rats with diabetic cardiomyopathy and its mechanism

作　　者：卫银芝[1] 熊世熙[2] 干学东[2] 龚斐[2] 曹建雷[2] 

机构地区：[1]湖北省黄石市中心医院老年病科,黄石市435000 [2]武汉大学中南医院心血管内科,武汉市430071

出　　处：《广西医学》2016年第6期766-769,共4页Guangxi Medical Journal

摘　　要：目的探讨替米沙坦对糖尿病心肌病(DCM)大鼠心肌超微结构的影响及其可能作用机制。方法 30只健康雄性Wistar大鼠,随机分成空白组10只和糖尿病组20只,糖尿病组用链脲佐菌素腹腔注射诱导建立DCM模型,建模成功后随机分成对照组及治疗组各10只。治疗组给予替米沙坦(20 mg/kg)灌胃治疗,空白组和对照组给予相同体积的生理盐水灌胃。给药16周后,光镜和电镜下观察各组大鼠心肌病理改变,采用脱氧核苷酸末端转移酶介导的d UTP缺口末端标记法检测心肌细胞凋亡情况,免疫组化法检测心肌细胞B淋巴细胞瘤因子-2(Bcl-2)、半胱氨酸-天冬氨酸蛋白酶-3(Caspase-3)及转化生长因子β1(TGF-β1)的表达情况。结果光镜下对照组心肌细胞排列紊乱,心肌细胞核出现融合、消失、间质纤维化等改变,电镜下对照组心肌线粒体肿胀、嵴断裂甚至空泡化,肌丝成分减少、断裂。与对照组相比,治疗组光镜下心肌病理改变减轻,电镜下心肌超微结构病理改变也减轻。与空白组相比,对照组左室指数明显升高、凋亡细胞增多、Bcl-2表达减少,Caspase-3的表达及TGF-β1的A值增加(P<0.05);与对照组比较,治疗组左室指数及凋亡指数下降、Bcl-2表达增加,而Caspase-3及TGF-β1的表达减少(P<0.05)。结论替米沙坦可以改善DCM大鼠心肌超微结构,延缓心室重构。Objective To explore the effect of telmisartan on myocardial uhrastructure in rats with diabetic cardiomyopathy （DCM） and its possible mechanism. Methods Thirty healthy male Wistar rats were randomly divided into blank group （n = 10） and diabetic group（n =20）. DCM model was established by transabdominal administration of streptozotocin in the diabetic group. After successful modeling, the diabetic group was randomly divided into control group and treatment group, with 10 rats in each group. Intragastric administration of telmisartan（ 20 mg/kg） was conducted in the treatment group, and intragastrie administration of normal saline was conducted in the blank group and control group. After 16 weeks of administration, the myocardial pathological change was observed under light microscope and transmission electron microscope in each group, myocardial apoptosis index was examined by terminal deoxynueleotidyl transferase-mediated d-UTP nick end labeling, and the expressions of B-cell lymphoma-2（ Bel-2 ） , Caspase-3 and transforming growth factor-β1 （TGF-β1） were detected by immunohistochemistry. Results In the control group,the arrangement of myocardial cells was irregular,and the changes including fusion,vanishment and interstitial fibrosis were found in nucleus of myocardium under light microscope. Besides, the myocardial mitochondria lined irregularly ,their cristae fractured and became vacuolation, and myofilaments decreased and fractured in the control group under transmission electron microscope. Compared with the control group,the pathological changes under light microscope and the myocardial ultrastructure under transmission electron microscope alleviated in the treatment group. Compared with the blank group,the left ventricular index and apoptosis index increased,the expression of Bcl-2 decreased, and the expression of Caspase-3 and A value of TGF-β1 increased in the control group （P 〈 0.05）. Compared with the control group,the left ventricular index and apoptosis index decreased

关 键 词：糖尿病心肌病 替米沙坦 心肌 转化生长因子β1 淋巴细胞瘤-2 半胱氨酸-天冬氨酸蛋白酶-3 大鼠 细胞超微结构 心室重构 

分 类 号：R362[医药卫生—病理学] R587.1[医药卫生—基础医学]