洛沙坦抑制急性心肌梗死大鼠心肌纤维化的作用机制  

Mechanisms of losartan for inhibition of myocardial fibrosis following myocardial infarction in rats

作　　者：邬真力[1] 许顶立[1] 邓烈华[1] 温勇伟[1] 黄鹏[1] 白书昌 苏亮[1] 

机构地区：[1]南方医科大学南方医院心内科,广东广州510515

出　　处：《南方医科大学学报》2008年第12期2260-2263,共4页Journal of Southern Medical University

摘　　要：目的观察洛沙坦对急性心肌梗死大鼠心肌组织中盐皮质激素受体(MR)mRNA及心肌纤维化的影响。方法结扎左冠状动脉致急性心肌梗死大鼠模型,随机分为急性心梗组和洛沙坦治疗组,而对照组为仅打开心包腔而未行冠状动脉结扎大鼠。在洛沙坦治疗4周时,用超声心动图和血流动力学指标评价心脏功能,心肌Masson染色法测定心肌胶原密度,放射性免疫法测定心肌组织中血管紧张素II(AngⅡ)、醛固酮(Ald)含量,实时荧光定量PCR检测心肌MRmRNA表达。结果(1)急性心梗组大鼠心肌组织中AngⅡ、Ald含量较对照组显著增加,心肌MRmRNA表达显著升高,同时心肌胶原密度显著增加(P<0.01)。(2)洛沙坦治疗4周后,治疗组大鼠心肌组织中AngⅡ、Ald较急性心梗组显著减低(P<0.05),MRmRNA表达显著降低,心肌胶原密度也有显著降低(P<0.01)。结论洛沙坦可以抑制急性心肌梗死大鼠心肌组织中Ald信号通路,并且还可能通过下调心肌MRmRNA表达来抑制心肌纤维化。Objective To investigate the effect of losartan on cardiac mineralocorticoid receptor （MR） mRNA in rats after acute myocardial infarction （AMI）. Methods AMI was induced in male SD rats by ligation of the left coronary artery. The survived rats were randomly divided into AMI group, losartan group, and sham-operated group. The cardiac functions of the rats were assessed by echocardiogram and hemodynamics, and the contents of angiotensin Ⅱ （Ang Ⅱ） and aldosterone （Aid） in the myocardial tissues were determined by radioimmunoassay. The collagen density in the myocardial tissues were calculated by Masson＇s trichrome staining and the expression of MR mRNA were determined by real-time quantitative fluorescent PCR. Results Both the contents of AngⅡ and Ald in the myocardial tissues increased significantly in AMI group compared with those in the sham-operated group （P〈0.01）. The expression of MR mRNA and collagen density in the myocardial tissues also increased significantly than that in sham-operated group （P〈0.01）. After four weeks of losartan treatment, the contents of AngⅡ and Aid in the myocardial tissues decreased significantly （P〈0.05） and the expression of MR mRNA was also considerably lowered （P〈0.01） in comparison with those in the AMI group. Treatment with losartan also resulted in significant decrease of the collagen density in the myocardial tissues. Conclusion Losartan may reduce reactive fibrosis not only by attenuating the Aid signaling pathway but also by decreasing the expression of MR.

关 键 词：急性心肌梗死 盐皮质激素受体 心肌纤维化 洛沙坦 血管紧张素Ⅱ 醛固酮 

分 类 号：R542.22[医药卫生—心血管疾病]