初探奥美沙坦减少大鼠心肌梗死后室性心律失常的机制

Primary study on mechanism of Olmesartan reducing ventricular arrhythmia in rats after myocardial infarction

目的评估血管紧张素受体拮抗剂奥美沙坦对心肌梗死后大鼠室性心律失常发生发展及对心肌梗死区连接蛋白43的表达变化的影响。方法 60只大鼠分为假手术组(Sham组)20只,急性心肌梗死模型组(MI组)20只和急性心肌梗死+奥美沙坦组(OM组)20只。超声心动图评价大鼠心脏功能,应用程序性电刺激检测大鼠室性心律失常发生情况,并测定各组大鼠心肌梗死边缘区和非梗死区连接蛋白43的m RNA及蛋白表达。结果与MI组相比,奥美沙坦可以改善心功能(t=1.85,P<0.01),减少心梗后室性心律失常的发生率(t=1.59,P<0.05);OM组心肌梗死边缘区和非梗死区连接蛋白43的m RNA表达量高于MI组(t=1.48,1.52,P<0.05),而其蛋白的表达量也在梗死边缘区高于MI组(t=1.45,P<0.05)。结论奥美沙坦可以改善心肌梗死后大鼠心功能,减少室性心律失常的发生率,这些可能都与奥美沙坦上调梗死边缘区和非梗死区连接蛋白43的表达有关。

Objective To evaluate the effect of angiotensin Ⅱ receptor blocker,olmesartan, on the incidence anddevelopment of ventricular arrhythmia and the expression of myocardial connexins（Cx） 43 in rats after myocardial infarction（MI）. Methods Sixty rats were divided into 3 groups： sham-operation group（n=20）, acute MI group（n=20） and acute MI＋OMgroup（n=20）. Echocardiography was employed to evaluate cardiac function, and programmed electrical stimulation（PES）experiment was used for the incidence of ventricular arrhythmias.The expression of Cx43 at m RNA and protein levels in the leftventricular border zone（BZ） and non-infarct zone（NIZ） were determined by real-time PCR and Western blotting, respectively.Results When compared with the rats from the MI group, olmesartan effectively improved the cardiac function（t =1.85, P〈0.01）,decreased the incidence of ventricular arrhythmia evoked by PES（t =1.59, P〈0.05）, and at the same time, significantlyimproved the m RNA expression levels of Cx43 in BZ（t =1.48, P〈0.05） and NIZ（t =1.52, P〈0.05） and the protein level of themolecule in BZ（t =1.45, P〈0.05）. Conclusion Olmesartan improves cardiac function in MI rats, and reduces the incidenceof PES-induced ventricular arrhythmia, which might be through up-regulating the myocardial Cx43 expression in BZ and NIZ.