目的:探讨早期介入运动训练对脑缺血大鼠脑缺血区血管新生的影响以及对酪氨酸激酶受体Tie-2信号转导通路促进血管新生的调节作用。方法:采用改良线栓法制作大鼠大脑中动脉缺血再灌注模型,将造模成功的大鼠随机分为手术对照组、手术+运动组,同时设立假手术组,并在术后24h后对运动组进行跑台训练。2周后,断头取脑,利用免疫组化方法标记Ⅷ因子检测比较各组大鼠脑缺血区微血管密度;Western Blot检测各组大鼠脑缺血区血管生成素受体Tie-2、总AKT、磷酸化AKT表达。结果:手术对照组微血管密度较假手术组有所升高,但无统计学意义;与手术对照组相比,手术+运动组微血管密度显著增加并具有统计学意义(P〈0.05)。各组大鼠缺血区总AKT、磷酸化AKT、Tie-2表达检测结果:3组总AKT无显著差异;与假手术组相比,手术对照组磷酸化AKT及Tie-2都有升高的趋势,但无统计学意义;手术+运动组较其它两组相比显著升高(P〈0.05)。结论:对脑缺血大鼠早期(缺血再灌注损伤24h后)进行2周跑台训练可上调梗死灶边缘区Tie-2受体的表达,促进下游P13K/AKT通路的相关蛋白磷酸化,启动该通路促进血管新生,增加脑缺血区微血管密度,从而改善大脑血液循环,达到脑保护的作用。
Objective To investigate the effect of treadmill training on the angiogenesis in affected brain area in rats with focal cerebral ischemia via the PI3K/AKT pathway. Methods Thirty rats were divided into 3 groups:sham group; control group ;treadmill training group(TM). The occlusion of left middle cerebral artery of male SD rats was induced by insertion of an intraluminal suture. Rats were killed after 2 weeks, and the angiogenesis was examined by means of immunohistochemical technique. The expression of Tie-2 and total-AKT/phospho-AKT was determined by Western blot. Results The data indicated that the angiogenesis and the expression of Tie-2 and phospho-AKT increased in control group as compared to the sham group,but there was no statistical significance between the two groups;while the number of expression of Tie-2 and phospho-AKT in the treadmill training group increased significantly as compared to the other two groups(P〈0.05). There was no significant difference in the expression of total-AKT in the three groups. Conclusion 2-week treadmill training could upregulate the expression of Tie-2,improve the phosphorylation of PI3K/ AKT pathway related proteins, and thus to switch on the pathway for facilitation of angiogenesis around the affected area of brain in rat with early stage of isehemia.