缬沙坦干预心肌梗死大鼠心室重构实验探究-.docVIP

缬沙坦干预心肌梗死大鼠心室重构实验探究* 　 【摘要】 目的 探讨缬沙坦在心肌梗死后大鼠心室重构的作用机制。方法 结扎大鼠冠状动脉复制急性心肌梗死模型和充血性心力衰竭的大鼠动物模型；TUNEL法检测心肌细胞凋亡，用SP免疫组织化学方法染色检测心肌Bax蛋白表达。结果 心肌梗死大鼠凋亡心肌细胞数明显增多，其促凋亡基因Bax蛋白表达较对照组亦明显增强，尤其是急性期呈高表达（P＜0.01）；缬沙坦干预虽能抑制部分Bax蛋白的表达量，但仍明显强于对照组（P＜0.05）。结论 心肌细胞凋亡与其Bax表达过高有关；缬沙坦可能通过阻断血管紧张素Ⅱ而部分抑制心肌梗死时心肌细胞凋亡的发生，从而减轻或逆转心室重构。 【关键词】 心肌梗死；心室重构；凋亡；Bax蛋白；缬沙坦 Experimental study on myocardial remodeling interfered with valsartan in myocardial infarction of rats 【Abstract】 Objective To determine potential mechanisms of the valsartan to cardiomyocyte apoptosis and Bax protein expression in myocardial infarction of rats.Methods Animal model of acute myocardial infarction were established by ligating the left anterior descending coronary artery of rats，myocyte apoptosis were estimated by terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL)，Bax protein expression of myocardium were semi-quantified by SP immunohistochemistry.Results Cell necrosis was the main manifestation in early stage，and then gradually increased the number of apoptotic cells and positively correlated to the expression of Bax protein，especially in acute stage (P＜0.01)；valsartan inhibited its expression to some extend (P＜0.05).Conclusion In infarcted myocardium，cardiomyocyte apoptosis is positively correlated to Bax protein expression，and they can be suppressed but not fully suppressed by the angiotensin II(Ang II) type 1 receptor blocker-valsartan.Valsartan can inhibit Ang Ⅱ and reduce the numbers of apoptotic cardiomyocyte.It is probably one of the mechanisms of the myocardial remodeling decreased by valsartan. 【Key words】 myocardial infarction；myocardial remodeling；apoptosis；Bax protein；valsartan 心室重构是发生充血性心力衰竭(CHF)的病理基础，其中心肌纤维排列紊乱、心肌细胞的丢失以及纤维结缔组织的增生是参与心室重构的主要病理过程。心肌细胞丢失包括细胞坏死和细胞凋亡。近年来心肌细胞凋亡在心肌缺血再灌注时的变化已有报道［1’’2］但在由急性心衰向慢性心衰的转变过程中，心肌细胞丢失的时域改变以及血管紧张素Ⅱ受体拮抗剂（angiotensin II receptor blockers，ARBS）—缬沙坦(valsartan)干预后的情况如何，目前尚不太清楚。本实验通过结扎大鼠冠状动脉前降支建立大鼠心肌梗死模型致大鼠心室重构，观察心肌梗死后发生心室重构的过程中心肌细胞凋亡和促凋亡基因Bax蛋白表达的时域变化规律及缬沙坦