尼可地尔对缺血性心力衰竭大鼠心功能的保护作用及机制

Protective effects of nicorandil on cardiac function in rats with ischemic heart failure and its mechanism

目的探讨尼可地尔对缺血性心力衰竭大鼠心功能和左室重构的保护作用及相关机制。方法将40只大鼠随机分为空白对照组(Con组)、尼可地尔组(NIC组)、生理盐水组(NS组)及假手术组(Sham组),每组10只,分别采取不同处理方式。记录各组大鼠体重、呼吸模式、活动量和毛色差异。术后8周所有大鼠行超声心动图检查。实验结束后对大鼠左心室前壁组织进行HE染色及电镜观察。检测心肌组织中p-Akt、Bcl-2、Bax蛋白的相对表达量。结果与Con组及Sham组相比,NS组及NIC组左心室射血分数(LVEF)、速度最大值(E)/心房收缩心室充盈速度最大值(A)(E/A)降低,NS组LVEF下降最多,差异有统计学意义(P<0.05)。左心室舒张末期容积(LVEDV)则呈相反趋势,3组间存在差异,NS组LVEDV最高,差异有统计学意义(P<0.05)。NS组左心室收缩末期容积(LVESV)、左室舒张末期内径(LVIDd)和左室收缩末期内径(LVIDs)高于NIC组和Sham组,差异有统计学意义(P<0.05)。Sham组大鼠心肌细胞排列规则,横纹清晰;NS组心肌细胞排列紊乱,形状不规则,同时还表现出明显的纤维组织增生。Sham组、NIC组的左心室/体重比值(LVW/BW)和肺脏重量指数(Lungw/Bw)均低于NS组,差异有统计学意义(P<0.05)。与Con组及Sham组相比,NS组p-Akt、Bcl-2及Bax蛋白相对表达量增加,差异有统计学意义(P<0.05)。NIC组p-Akt、Bcl-2蛋白相对表达量高于NS组,但Bax蛋白表达量下降,差异均有统计学意义(P<0.05)。结论尼可地尔可通过改善心功能和左室重塑对缺血性心力衰竭大鼠起到保护作用,这可能与抑制Bax蛋白表达有关。

Objective To investigate the protective effect of nicodil on cardiac function and left ventricular remodeling in ischemic heart failure rats and its related mechanism.Methods Forty rats were randomly divided into blank control group(Con group),nicodil group(NIC group),normal saline group(NS group)and Sham operation group(Sham group),with 10 rats in each group,and different treatment methods were adopted.The differences of body weight,respiratory pattern,activity and hair color were recorded.Echocardiography was performed in all rats 8 weeks after operation.After the experiment,the anterior wall tissue of the left ventricle of rats was observed by HE staining and electron microscopy.The relative expression levels of p-Akt,Bcl-2 protein and Bax in myocardial tissue were detected.Results Compared with Con group and Sham group,left ventricular ejection fraction(LVEF)and ratio of maximum velocity(E)to atrial contraction maximum ventricular filling velocity(A)(E/A)in NS group and NIC group were significantly decreased,and LVEF in NS group had the most decrease(P<0.05).The left ventricular end-diastolicvolume(LVEDV)showed an opposite trend,with significant differences among the three groups,and the NS group had the highest LVEDV(P<0.05).Left ventricular end-systolic volume(LVESV),left ventricular end-diastolic diameter(LVIDd)and left ventricular end-systolic diameter(LVIDs)in NS group were significantly higher than those in NIC group and Sham group(P<0.05).In the Sham group,the myocardial cells were arranged regularly and the transverse lines were clear;in the NS group,the myocardial cells were disordered and irregular in shape,and obvious fibrous tissue proliferation was also observed.However,compared with NS group,these abnormalities in NIC group were significantly reduced and myocardial fiber structure tended to be normal.The ratio of left ventricular weight(LVW)to body weight(LVW/BW)and lung mass index(Lungw/Bw)in Sham group and NIC group were significantly lower than those in NS group(P<0.05).Compared with Con group and Sham group,the relative expression levels of p-Akt protein,Bcl-2 protein and Bax protein in NS group were significantly increased(P<0.05).The relative expression levels of p-Akt protein and Bcl-2 protein in NIC group were significantly higher than those in NS group,but the expression level of Bax protein was significantly decreased(P<0.05).Conclusion Nicorandil can protect rats with ischemic heart failure by improving cardiac function and left ventricular remodeling,which may be related to the inhibition of Bax protein expression.