重组胎盘生长因子对大鼠急性心肌梗死后细胞凋亡的影响

Effects of rPlGF on the Cardiomyocyte Apoptosis in the Rats with Acute Myocardial Infarction

目的研究重组胎盘生长因子(recombinant placental growth factor,r Pl GF)对大鼠急性心肌梗死后心肌细胞凋亡的影响并探讨其可能的作用机制。方法采用结扎冠状动脉的方法建立大鼠急性心肌梗死模型,取40只模型大鼠随机分为模型组和r Pl GF治疗组,并设假手术组,尾静脉注射给药。4周后,通过高频率超生影像系统检测舒张末期左心室内径(LVIDd)和收缩末期左心室内径(LVIDs)、短轴缩短率(FS)、射血分数(EF)、每搏排出量(SV);TTC染色法计算心肌梗死面积,TUNEL法观察心肌细胞凋亡状况,RT-PCR法测定心肌组织bcl-2 mRNA、Bax mRNA表达,Western blot法测定心肌组织caspase-3、NF-κB蛋白表达;比色法测定心肌组织中抗氧化酶活性和丙二醛(MDA)含量。结果与模型组比较发现经r Pl GF治疗能够显著降低急性心肌梗死大鼠LVIDd和LVIDs,提高FS、EF和SV;降低心肌组织梗死面积,显著降低心肌细胞凋亡指数(apoptosis index,AI)、明显改善心肌细胞凋亡状况,上调bcl-2 mRNA表达并下调Bax mRNA表达、显著提高bcl-2/Bax比值,显著降低caspase-3、NF-κB蛋白表达量,显著提高抗氧化酶(SOD、CAT)活性并显著降低MDA含量,差异均具有统计学意义(P<0.05,P<0.01)。结论 r Pl GF具有抑制大鼠急性心肌梗死后细胞凋亡的作用,其机制可能与r Pl GF改善心功能、调节凋亡相关基因蛋白表达以及抑制氧化应激损伤有关。

Objective To investigate the effects of recombinant placental growth factor（rPlGF） on the cardiomyocytes apoptosis in the rats with acute myocardial infarction. Methods The rat models with acute myocardial infarction were made by clamping the artery. 40 rat models were randomly devided into model control group and rPlGF treated group.sham operation group was set. The drugs were given by tail vein injection. 4 weeks later, the LVIDd, LVIDs, FS, EF, SV were detected by high frequency ultrasound imaging system. The areas of myocardial infarction was analysised by TTC staining. The cardiomyocyte apoptosis was observed by TUNEL. The expression of bcl-2 mRNA, Bax mRNA were determined. The expression of caspase-3, NF-κB were examined by Western blotting. The activity of antioxidase and the content of MDA in myocardial tissue were determined. Results Compared with model control group, the LVIDd, LVIDs in rPlGF treated group were significantly decreased, the FS, EF, SV were significantly increased; the myocardial infarction areas was significantly decreased, the myocardial cardiomyocyte apoptosis were significantly improved and the AI were significantly decreased, the expression of bcl-2 mRNA was significantly up-regulated and the Bax mRNA was significantly down-regulated, the ratio of bcl-2/Bax was significantly increased, the expression of caspase-3 and NF-κB protein were significantly decreased; the activity of SOD, CAT in myocardial tissue were significantly increased and the activity of MDA was significantly decreased. All of the difference above were significant（P〈0.05, P〈0.01）. Conclusion rPlGF has inhibitive effects on the cardiomyocytes apoptosis in the rats with acute myocardial infarction, which perhaps related to its effects of improving heart function, altering the expression of apoptosis-related genes, proteins and reducing oxidative stress.