福辛普利对慢性心力衰竭大鼠心肌细胞凋亡及相关基因表达的影响

谢亚芹，赵娟，李秀华，冯翔宇



福辛普利对慢性心力衰竭大鼠心肌细胞凋亡及相关基因表达的影响

谢亚芹，赵娟，李秀华，冯翔宇

摘要

关键词福辛普利；心力衰竭；细胞凋亡；凋亡相关基因

作者单位:067000 河北省承德市，承德医学院 病理生理学教研室(谢亚芹、赵娟)； 承德医学院附属医院 老年病科(李秀华、冯翔宇)

Effect of Fosinppril on Myocardial Cell Apoptosis and Apoptosis-associated Gene Expression in Chronic Heart Failure Rats

XIE Ya-qin,ZHAO Juan,LI Xiu-hua,FENG Xiang-yu.
Department of Pathophysiology,Chengde Medical College,Chengde(067000),Hebei,China
Corresponding Author:XIE Ya-qin,Email:xieyq1983@126.com

Abstract

Objective:To investigate the effects of fosinppril on myocardial cell apoptosis and apoptosis-associated gene expression in chronic heart failure(CHF)rats.

Methods:CHF model was established by partially banding of abdominal aorta superior to renal artery.The experimental rats were randomly divided into 3 groups:Sham operation group and CHF group,the rats in both groups received stomach normal saline;Fosinopril group,the rats received stomach fosinopril 10 mg/kg•d.n=10 in each group and all animals were treated for 8 weeks.LVEDP,±dp/dtmaxand LVMI were examined,left ventricular myocardial cell apoptotic index(AI)was measured by TUNEL method,Bcl-2 and Bax protein levels were detected by immunohistochemistry and caspase-3 protein expression was assessed by Western blotting.

Results:Compared with Sham operation group,CHF group had increased LVEDP,LVMI,AI,elevated protein expressions of Bax and Caspase-3,P<0.01;while decreased ±dp/dtmax,reduced protein expression of Bcl-2 and the ratio of Bcl-2/Bax,P<0.01.Compared with CHF group,Fosinopril group presented decreased LVEDP,LVMI,AI,reduced protein expressions of Bax and Caspase-3,P<0.01;while increased ±dp/dtmax,elevated protein expression of Bcl-2 and the ratio of Bcl-2/Bax,P<0.01.Conclusion:Fosinopril may inhibit myocardial cell apoptosis which occurred during CHF,by up-regulating Bcl-2 expression and down-regulating expressions of Bax and Caspase-3 in CHF rats,therefore improve the cardiac function.

Key words Fosinopril;Hear failure;Apoptosis;Apoptosis-associated gene

(Chinese Circulation Journal,2016,31:285.)

慢性心力衰竭是各种病因导致心脏疾病的严重阶段及最终归宿，也是心脏疾病患者最主要的死亡原因。近年来有研究证明[1]，长效血管紧张素转化酶抑制剂（ACEI）类药物在治疗高血压的同时可使心肌肥厚逆转，使扩大的心脏恢复正常，降低心脏负荷，改善心室功能，降低心力衰竭的死亡率。但其能否有效抑制长期慢性压力超负荷引起的心力衰竭心肌细胞凋亡仍需进一步研究。本研究将以肾上腹主动脉缩窄方式建立慢性压力负荷型心力衰竭动物模型，分析福辛普利对慢性心力衰竭大鼠心肌细胞凋亡及相关调节基因表达的影响，探讨其在积极逆转心肌受损，改善心力衰竭进程中的作用，为临床药物治疗的研究提供理论基础。

1　材料与方法

材料： 2014-01至2015-01选取清洁级雄性Wistar大鼠35只,购自北京华阜康生物科技股份有限公司（合格证编号：2009-0004）；福辛普利(10 mg)商品名：蒙诺，购自中美上海施贵宝制药有限公司；脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）细胞凋亡检测试剂盒购自美国罗氏（Roche）公司；B细胞白血病/淋巴瘤相关抗原2（Bcl-2）、B细胞白血病/淋巴瘤相关抗原相关X（Bax）和半胱氨酸天冬氨酸蛋白酶3 （Caspase-3）兔抗多克隆抗体均购自北京博奥森生物技术有限公司；……