游泳对心肌梗死大鼠心脏微血管的保护作用及机制研究

关键词：游泳  心肌梗死  剪切力  心脏微血管  凋亡

Keywords:swimming  myocardial infarction  shear stress  cardiac microvasculature  apoptosis

摘要：

      摘要 目的：研究游泳对心肌梗死（myocardial infarction，MI）大鼠康复阶段心脏微血管的保护作用及机制。 方法：选用Wistar大鼠（160—180g）80只，采用随机区组设计法分成4组：假手术组、模型组、游泳组、地奥心血康组，每组20只。通过结扎左冠状动脉主干制备MI模型，假手术组除不结扎冠状动脉外，其余操作与模型组动物完全相同。MI模型制备结束后14天，游泳组大鼠进行游泳训练，共计8周。地奥心血康组按照150 mg/kg·d灌胃给药，连续给药8周，模型组和假手术组同样方法灌胃相同体积生理盐水。采用超声心动图系统和BL—420F生物机能实验系统检测心功能及心电图；凝胶墨汁实验检测心脏微血管密度；Western Blot检测Caspase-3、PECAM-1、PI3K、p-PI3K、AKT、p-AKT、eNOS、p-eNOS的蛋白表达；NO试剂盒测心脏组织中NO的含量。 结果：游泳组及地奥心血康组较模型组ST段显著降低（P=0.002，P=0.000）；超声结果显示游泳组及地奥心血康组较模型组左室射血分数（LVEF）显著升高（P=0.038，P=0.003），游泳组及地奥心血康组左室短轴缩短率（LVFS）较模型组显著升高（P=0.028，P=0.000）；HE结果表明游泳及地奥心血康显著减小了模型大鼠的心脏梗死面积；Western blot结果显示游泳组及地奥心血康组较模型组Caspase-3蛋白表达量显著下调（P=0.035，P=0.000）；此外，游泳组及地奥心血康组心脏微血管密度较模型组显著增大（P=0.015，P=0.000）；同时，Western Blot结果显示游泳组较模型组PECAM-1的蛋白表达量显著上调（P=0.025），游泳组较模型组p-PI3K的蛋白表达量显著上调（P=0.013），游泳组较模型组p-AKT的蛋白表达量显著上调（P=0.02），游泳组较模型组p-eNOS的蛋白表达量显著上调（P=0.02）；此外，游泳组较模型组NO含量显著升高（P=0.011）。 结论：游泳增加MI大鼠心脏微血管剪切力，激活PECAM-1/PI3K/AKT/eNOS信号通路，促进NO释放，增加梗死区域心脏微血管血流灌注量，抑制心肌细胞凋亡，从而改善MI大鼠的预后。

Abstract:

      Abstract Objective：To investigate the protective effect and mechanism of swimming on cardiac microvasculature in rats with myocardial infarction (MI). Method：Eighty Wistar rats (160-180g) were randomly divided into 4 groups： sham operation group， model group， swimming group， and Diaoxinxuekang group， with 20 in each group. The MI model was prepared by ligating the main coronary artery of the left coronary artery. The operation in the sham operation group was identical to that in the model group except that the coronary artery was not ligated. Fourteen days after the completion of MI model preparation， the swimming training time of rats in the swimming group was 8 weeks. Cardiac function and electrocardiogram were detected by echocardiography system and BL-420F biological function experiment system. Cardiac microvascular density was measured by gel ink assay. The protein expressions of Caspase-3， PECAM-1， PI3K， p-PI3K， AKT， p-AKT， eNOS and p-eNOS were detected by Western blot. The content of NO in the heart tissue was measured by the kit. Result：ST segment in the swimming group or Diaoxinxuekang group was significantly lower than that in the model group (P=0.002， P=0.000). Small animal ultrasound results showed that LVEF value in the swimming group or Diaoxinxuekang group was significantly higher than that in the model group (P=0.038， P=0.003， LVFS value in the swimming group or Diaoxinxuekang group was significantly higher than that in the model group (P=0.028， P=0.000). HE results showed that swimming and Diaoxinxuekang significantly reduced the infarct area of the model rats. Western Blot results showed that the expression of Caspase-3 protein in the swimming group or Diaoxinxuekang group was significantly lower than that in the model group (P=0.035， P=0.000). In addition，the cardiac microvascular density in the swimming group or Diaoxinxuekang group was significantly higher than that in the model group (P=0.015， P=0.000). Meanwhile， Western Blot results showed that the protein expression level of PECAM-1 in the swimming group was significantly up-regulated compared with that in the model group (P=0.025). The expression level of p-PI3K in the swimming group was significantly up-regulated compared with that in the model group (P=0.013). The protein expression of p-AKT in the swimming group was significantly higher than that of the model group (P=0.02). The protein expression of p-eNOS in the swimming group was significantly increased compared with that in the model group (P=0.02).In addition， NO content in the swimming group was significantly higher than that in the model group (P=0.011). Conclusion： Swimming can increase cardiac microvascular shear stress， activate PECAM-1/PI3K/AKT/eNOS signaling pathway， promote NO release， increase cardiac microvascular perfusion in infarcted area， inhibit cardiac myocyte apoptosis， and thus improve the prognosis of MI rats.