KATP通道开放剂对脑梗死后突触可塑性的影响

Effects of KATP channel opener on synaptic plasticity after ischemic stroke

目的观察KATP通道开放剂尼可地尔对脑梗死后突触形成相关因子SYP和GAP43的影响,探讨其对脑梗死后突触可塑性的影响及机制。方法将大鼠随机分为三组:假手术+溶剂组、脑梗死+溶剂组、脑梗死+尼可地尔组,每组34只。线栓法建立大脑中动脉闭塞(MCAO)模型。尼氏染色评估梗死体积;术后1、3、7、14 d进行神经功能缺损评估;水迷宫测试检测学习记忆功能;PCR以及Western blot检测SYP和GAP43的mRNA和蛋白水平。结果与脑梗死+溶剂组相比,脑梗死+尼可地尔组脑梗死体积明显减少,神经功能缺损明显改善,学习记忆功能明显改善,SYP和GAP43的mRNA及蛋白水平增加。差异均具有统计学意义(P<0.05)。结论尼可地尔促进了MCAO大鼠的神经缺损功能的恢复,可能与增加了SYP和GAP43的表达,从而促进脑梗死后的突触可塑性有关。

Objective To observe the effect of nicorandil,an ATP⁃sensitive potassium channel opener,on the expression of SYP and GAP43 in adult rats with cerebral ischemia⁃reperfusion,and to explore the mechanism of nicorandil in synaptic plasticity.Methods Rats were divided into Sham+Vehicle group(n=34),MCAO+Vehicle group(n=34)and MCAO+Nicorandil group(n=34)according to the randomization principle.Middle cerebral artery occlusion(MCAO)model procedure was used by the intraluminal suture model.Nissl staining was used to assess the infarct volume,and modified neurological severity scores(mNSS)were calculated to assess the neurological function on the 1st,3rd,7th and 14th days after surgery.Morris Water Maze test was used to detect the learning and memory function.PCR and Western blot were used to detect the mRNA and protein levels of SYP and GAP43.Results Compared with those in MCAO+Vehicle group,the infarct volume of MCAO+Nicorandil group was significantly reduced;neurological impairment was significantly ameliorated;learning and memory disorders were improved;and the mRNA and protein levels of SYP and GAP43 were increased.The differences were statistically significant(P<0.05).Conclusion The treatment with Nicorandil can promote functional recovery of neurological deficits in MCAO rats.The possible mechanism is closely related to the up⁃regulation of expression of SYP and GAP43,thus to improve synaptic plasticity.