重复经颅磁刺激对脑梗死后海马PSD-95和GAP-43表达的影响及其机制研究

目的:观察高频重复经颅磁刺激(rTMS)对脑梗死大鼠缺血侧海马突触后致密物质-95(PSD-95)和生长相关蛋白-43(GAP-43)表达的影响及其可能机制。方法:SD雄性成年大鼠20只,分为模型组(A组)和rTMS组(B组)各6只,rTMS+NS(normal saline)组(C组)和rTMS+阻滞剂H89组(D组)各4只,建立脑梗死模型,给予7d的20Hz rTMS治疗,应用Western Blot方法检测A、B组缺血侧海马PSD-95和GAP-43表达并观察超微结构,进一步研究给予C、D组间蛋白激酶A-环磷酸腺苷反应元件结合蛋白(pCREB)、PSD-95和GAP-43表达变化。结果:与A组相比,B组PSD-95和GAP-43表达增加(P0.01),电镜下突触体积增大,突触前后膜电子致密区增宽,电子密度和突触囊泡数量增加。D组pCREB、PSD-95、GAP-43表达较C组均减少(P0.01)。结论:rTMS有可能通过对PKA-CREB信号通路调节来促进脑梗死后海马PSD-95、GAP-43的表达。

Effects and mechanism of repetitive transcranial magnetic stimulation (rTMS) on expression of PSD-95 and GAP-43 in hippocampus of rats with cerebral infarction

Objective:To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on the expression of PSD-95 and GAP-43 and its mechanism in the ischemic hippocampus of rats with cerebral infarction.Methods:A total of 20 SD rats were divided into model control group(A),rTMS group(B),with 6 cases in every group,rTMS+NS group(C) and rTMS+H89 group(D),with 4 cases in every group.Reperfusion model with middle cerebral artery occlusion was established.rTMS of 20Hz was given to successful models for 7 days.Utrastructures of the ischemic CA1 and expression changes of PSD-95 and GAP-43 in rats of group A and B were investigated under the transmission electron microscopy and western blot respectively.The expression of pCREB,PSD-95 and GAP-43 were detected in the group C and D.Results:As compared with group A,the PSD-95 and GAP-43 expression levels were increased in group B(P<0.01).Under the transmission electron microscopy,the synaptic volume was increased,the anterior and posterior electron dense areas of the synapse were widened,the electron density and synaptic vesicles quantity were increased in group B.As compared with group C,the expression levels of pCREB,PSD-95and GAP-43 were decreased in group D(P<0.01).Conclusion:rTMS could promote PSD-95 and GAP-43 expression in the ischemic hippocampus after cerebral ischemia probably by regulating the PKA-CREB pathway.