早期运动干预对脑缺血大鼠脑神经髓鞘的影响及机制研究

Effect and mechanism of early exercise intervention on cerebral nerve myelin in rats with cerebral ischemia

目的 探讨早期运动干预通过抑制内质网应激诱导的细胞凋亡对脑缺血大鼠脑神经髓鞘损伤的影响。方法 18只SD大鼠随机分为假手术(SHAM)组,大脑中动脉闭塞静息(MCAO-SED)组、大脑中动脉闭塞运动(MCAO-EX)组,每组6只。除SHAM组外,其他各组采用改进的Longa线栓塞法制备大脑中动脉闭塞模型。造模后MCAO-EX组大鼠置于跑步机上进行运动干预28 d。采用改良的神经功能缺损评分(mNSS)评估神经功能,MRI扫描(T2)检测脑梗死体积,免疫荧光染色检测髓磷脂碱性蛋白(MBP)表达,透射电子显微镜观察髓鞘的结构,Western blot法检测内质网应激相关蛋白表达,TUNEL染色检测细胞凋亡。结果 干预28 d后,同MCAO-SED组比,MCAO-EX组神经功能恢复良好,梗死体积减少,髓鞘完整性增加,MBP荧光强度表达增加,MBP的表达水平增加,同时转录激活因子6(ATF6)、磷酸化肌醇需求酶1(p-IRE1)、磷酸化蛋白激酶R样内质网激酶(p-PERK)、活化的胱天蛋白酶-3(cleaved caspase 3)蛋白的表达水平显著降低,细胞凋亡减少。结论 早期运动可抑制内质网应激诱导的细胞凋亡,促进脑神经髓鞘修复,减少梗死面积,改善神经功能。

Objective To investigate the effect and potential mechanism of early exercise intervention on cerebral myelin in cerebral ischemia rats.Methods A total of 18 SD rats were randomly divided into the sham group,the middle cerebral artery occlusion resting group(MCAO-SED)and the middle cerebral artery occlusion exercise group(MCAO-EX),with 6 rats in each group.Except the sham group,the middle cerebral artery occlusion model was prepared by modified Longa line embolization method in other groups.After modeling,rats in the MCAO-EX group were placed on a treadmill for exercise intervention for 28 days.Neurological function was assessed by modified neural function deficit score(mNSS).Infarct volume was detected by MRI scanning(T2),myelin basic protein(MBP)expression was detected by immunofluorescence.Myelin sheath structure was detected by transmission electron microscopy.Western blot assay was used to detect endoplasmic reticulum stress-related protein expression.Apoptosis was detected by TUNEL staining.Results After 28 days of intervention,compared with the MCAO-SED group,the nerve function recovered well in the MCAO-EX group,infarct volume decreased,myelin integrity increased,MBP fluorescence intensity expression increased and MBP expression level increased.The expression levels of ATF6,p-IRE1,p-PERK and cleaved caspase 3 were significantly decreased,and apoptosis was reduced.Conclusion Early exercise can inhibit endoplasmic reticulum stress-induced apoptosis,promote cerebral myelin repair,reduce infarct size and improve nerve function.