单核细胞趋化因子-1在等长收缩运动促进大鼠缺血心肌侧支动脉生成中的作用

目的:探讨单核细胞趋化因子-1(MCP-1)在等长收缩运动训练促进缺血心肌侧支动脉生成中的作用。方法:将造模成功的24只雄性SD大鼠,体重(200±20)g,随机分为4组:对照组(CG)、心肌缺血组(MI)、运动训练组(ET)、MCP-1抑制剂组(LG),每组均有6只大鼠。CG组连续2周皮下注射生理盐水;MI组连续2周皮下注射异丙肾上腺素(10mg/kg/d),造成心肌缺血;ET组连续2周皮下注射异丙肾上腺素并且进行等长收缩运动训练;LG组在ET组的基础上进行MCP-1抑制剂来氟米特灌胃。训练8周结束后,麻醉大鼠,取左心室心肌,采用微球法测定缺血区心肌相对侧支循环血流量(RCBF);采用免疫组化法测定缺血区心肌小动脉密度和单核细胞数量;以Western blot和荧光定量PCR法测定缺血心肌中MCP-1的蛋白及mRNA的表达。结果:ET组大鼠的相对侧支血流量(RCBF)、小动脉密度(AD)明显高于其余3组(P0.001),LG组的RCBF和AD与MI组相比无显著性差异;ET组大鼠缺血心肌中单核细胞数量、MCP-1 mRNA以及MCP-1蛋白表达均显著高于其余各组(P0.001),而LG组大鼠缺血心肌中单核细胞数量、MCP-1 mRNA以及MCP-1蛋白表达与MI组相比无显著性差异。结论:持续8周的等长收缩运动训练可以增加大鼠缺血心肌中MCP-1的表达,从而促进缺血心肌侧支动脉的生成。

Effects of MCP-1 in isometric exercise training promotes the collateral artery formation in mice with myocardial ischemia

Abstract Objective: To investigate the role of monocyte chemoattractant protein-1 in the progress that isometric exercise training improves arteriogenesis. Method: Twenty-four male Sprague-Dawley rats were used, weighing (200±20)g. The rats were randomized into control group (CG), myocardial ischemia group (MI), exercise training group (ET), MCP-1 inhibitor group (LG). There were 6 rats in each group. Rats were continuously administered 10mg/kg subcutaneously isoproterenol for successive 2 weeks to establish the myocardial ischemia model. Successfully modeled rats were in groups MI, ET and LG. Isometric exercise training were performed in group ET and LG. The rats in group LG were given MCP-1 inhibitor leflunomide by gavage. After 8 weeks of training, the left ventricular myocardium was extracted and relative collateral blood flow (RCBF) was measured by microspheres. Artery density (AD) and monocytes were measured by immunohistochemistry analysis. Western blot analysis and real-time quantitative PCR were performed to assay protein and mRNA of MCP-1. Result: RCBF and AD increased significantly in group ET as compared to the rest groups. RCBF and AD in group LG showed higher than that in group MI but not significant. The number of monocytes, MCP-1 mRNA and MCP-1 expression were significantly elevated in ischemic myocardium of group ET. Interestingly, the number of monocytes, MCP-1 mRNA and MCP-1 expression showed lower than that in group MI but also not significant. Conclusion: Eight weeks of isometric exercise training can increase the expression of MCP-1 in ischemic myocardium and promote the arteriogenesis.