生长素释放肽对心力衰竭大鼠心肌细胞抗凋亡机制的初步研究

Preliminary Research for the Effect of Growth Hormone Releasing Peptide on Myocardial Cell Apoptosis in Heart Failure Rats

目的:探讨生长素释放肽(GHRP)对心力衰竭(心衰)大鼠心肌细胞抗凋亡机制。方法:40只雄性SD大鼠,随机分为4组:正常对照组、假手术组、心衰模型组、GHRP治疗组,每组10只。通过结扎冠状动脉左前降支缺血诱导大鼠建立心衰模型。术后各组大鼠正常饲养4周,检测心脏功能,观察各组大鼠心肌细胞形态学改变。免疫蛋白印迹(Western blot)方法检测各组心肌细胞Smac/DIABL0蛋白和B型白细胞/2型淋巴细胞样蛋白(Bcl-2)表达情况。应用流式细胞(FCM)技术检测各组大鼠心肌细胞凋亡情况。比较各组间各指标差异,探讨GHRP对心衰大鼠心肌细胞抗凋亡机制。结果:GHRP治疗组大鼠的心脏扩张程度较心衰模型组轻,而左心室射血分数比心衰模型组高(P<0.05)。GHRP治疗组的心肌细胞病理改变程度较心衰模型组轻(P<0.05)。GHRP治疗组Smac/DIABLO表达水平较心衰模型组显著降低(P<0.05),心衰模型组Bcl-2水平较其余三组明显降低(P<0.05)。GHRP治疗组Bcl-2表达水平较正常对照组明显增高(P<0.05)。心衰模型组与GHRP治疗组心肌细胞FCM凋亡指数比较,差异有统计学意义(P<0.05)。结论:GHRP具有抑制心肌细胞凋亡的抗心衰作用,其机制可能部分通过促进Bcl-2抗凋亡蛋白表达,抑制由Smac/DIABLO介导的线粒体途径的心肌细胞凋亡实现。

Objective： To explore the effect of growth hormone releasing peptide （GHRP） on myocardial cell apoptosis in heart failure （HF） rats. Methods： Rat＇s HF model was established by the ligation of left anterior descending coronary artery induced ischemia. 40 male SD rats were randomly assigned into 4 groups： Normal control group, Sham operation group, HF group and GHRP treated HF group, n=10 in each group and the rats were fed for 4 weeks after the operation. Cardiac function was examined and myocardial cell morphology was observed; protein expressions of Smac/D1ABL0 and Bcl-2 were measured by Western blot analysis; cell apoptosis was evaluated by FCM technique. The differences for above parameters were compared among groups to explore the effect of GHRP on myocardial cell apoptosis in HF rats. Results： Compared with HF group, GHRP treated HF group showed the less heart dilation, higher LVEE lighter pathological changes in myocardial cells and decreased protein expression of Smac/DIABL0, all P〈0.05. Bcl-2 level was lower in HF group than the other 3 groups, P〈0.05. Compare with Normal control group, GHRP treated HF group had elevated Bcl-2 level, all P〈0.05. Myocardial cell apoptosis index was different between HF group and GHRP treated HF group, P〈0.05. Conclusion： The effect of GHRP on anti-HF should be via inhibiting myocardial cell apoptosis; the mechanism may partly be through promoting Bcl-2 protein expression and depressing Smac/DIABLO mediated mitochondrial pathway of apoptosis.