尼可地尔对大鼠脑梗死后神经元再生的影响

Effects of nicorandil on neuronal regeneration in rats following cerebral infarction

目的:探讨尼可地尔对脑梗死大鼠神经元再生的作用及机制。方法:90只SD雄性大鼠分为:假手术组、脑梗死组和尼可地尔组,每组30只。线栓法建立大鼠大脑中动脉闭塞(MCAO)模型。术后第1、3、7、14天采用Zea-Longa法观察神经功能缺损,术后第3天通过检测脑含水量来测定脑水肿程度;采用TUNEL法检测细胞凋亡,免疫荧光双染法观察BrdU/NeuN阳性细胞数,RT-PCR检测NeuN mRNA的表达,Western blot检测NeuN蛋白的表达。结果:与假手术组相比,脑梗死组和尼可地尔组大鼠脑含水量升高,凋亡细胞数增加,BrdU/NeuN阳性细胞数增加,NeuN mRNA和蛋白的表达升高(P<0.05);与脑梗死组相比,尼可地尔组大鼠脑含水量降低,神经功能缺损改善,脑梗死周围区凋亡细胞数减少,BrdU/NeuN阳性细胞数增加,NeuN mRNA和蛋白的表达升高(P<0.05)。结论:尼可地尔可以减轻脑水肿,减少凋亡,促进神经功能恢复,促进神经再生,进而达到对脑梗死大鼠的神经保护作用。

Aim:To investigate the neuroprotective effects and mechanisms of nicorandil on rats after cerebral infarction.Methods:A total of 90 male SD rats were allocated into sham group(n=30),model group(n=30)and nicorandil group(n=30)according to the randomization principle.Middle cerebral artery occlusion(MCAO)model was constructed by the intraluminal suture method.Zea-Longa method was used to assess the neurological function on the 1st,3rd,7th and 14th day after surgery.Brain water content was detected to measure cerebral edema,and TUNEL was used to detect cell apoptotic.The positive BrdU/NeuN cells was detected by immunofluorescence staining.RT-PCR and Western blot were used to detect the mRNA and protein levels of NeuN.Results:Compared with sham group,the brain water content was increased,the number of apoptotic cells and BrdU/NeuN positive cells was increased,and the mRNA and protein expression levels of NeuN were increased in model group and nicorandil group(P<0.05).Compared with model group,the brain water content of nicorandil group was significantly decreased,the neurological impairment was significantly ameliorated,the number of apoptotic cells was reduced,the number of BrdU/NeuN positive cells was increased,and the mRNA and protein expression levels of NeuN were increased(P<0.05).Conclusion:Nicorandil treatment could achieve neuroprotective effect on rats with cerebral infarction by reducing cerebral edema,reducing apoptosis,improving neurological function recovery and promoting nerve regeneration.