功能性电刺激促进急性脑梗死大鼠脑部内源性神经干细胞增殖的研究

Endogenous proliferation of neural stem cells within the brain induced by functional electrical stimulation in rats with acute cerebral infarction

目的研究功能性电刺激（FES）对急性脑梗死大鼠行为学和内源性神经干细胞（NSCs）增殖的影响。探讨FES治疗改善脑梗死后神经功能的机制。方法54只成年雄性SD大鼠按随机数字表法分为FES治疗组、安慰刺激组和假手术组（每组各18只）。行大脑中动脉阻断（MCAO）制作局灶性脑梗死模型后第3天，FES治疗组开始接受FES治疗（10min／d，每天1次），安慰刺激组阻断动脉但不予电刺激。在FES治疗后3、7、14d评价大鼠行为学功能（平衡木行走测评、转棒上行走测评、网屏试验1，免疫组织化学法观察大鼠海马齿状回和室管膜下区NSCs巢蛋白（nestin）的表达水平．Western blot法检测梗死侧脑组织nestin总蛋白表达量。结果FES治疗组网屏试验评分在治疗后14d时低于安慰刺激组，比较差异有统计学意义（P〈0．05）。FES治疗组大鼠海马齿状回和室管膜下区nestin阳性细胞数和梗死侧脑组织nestin总蛋白表达量在治疗后7d、14d时均高于安慰刺激组和假手术组，比较差异有统计学意义（P〈0．05）。结论FES能促进急性脑梗死大鼠脑部内源性NSCs的增殖并改善大鼠行为学功能，这可能是FES治疗改善脑梗死后神经功能的机制之一。

Objective To investigate the effects of functional electrical stimulation （FES） on endogenous proliferation of the neural stem cells within the brain and the behaviors in rats with acute cerebral infarction and explore the FES therapeutic mechanism on improving the neural function after the cerebral infarction. Methods Fifty-four SD adult male rats were randomly allocated into FES treatment group, placebo stimulation group and sham-operated group （n=18）. Focal cerebral infarction models were induced by the performent of middle cerebral artery occlusion （MCAO） in rats; the FES treatment group began receiving the FES （10 min/d, once dairy） and the placebo stimulation group did not give any special treatment since the 3rd day of the successful model inducement. The expression of nestin positive ceils in the hippocampus subgranular zone and subventricular zone was examined by immunohistochemistry staining and the expression of nestin protein at ischemia side was detected by Western blot analysis on the 3rd, 7th and 14th d after MCAO; meanwhile, the behavior functions of rats at various time points were evaluated. Results The number ofnestin positive cells in the hippocampus subgranular zone and subventricular zone and the expression ofnestin protein from ischemia side brain in the FES treatment group significantly increased than those in the placebo stimulation group on the 7th and 14th d after MCAO （P〈0.05）. And statistical difference was noted on the 14th d on the behavior functional evaluation between the FES treatment group and the placebo stimulation group （P〈0.05）. Conclusion FES may enhance the endogenous proliferation of the neural stem cells within the brain in rats with acute cerebral infarction and improve the behavior function in rats, which may be one of the mechanisms of FES on improving the neural function after cerebral infarction.