摘要
目的:探讨三七总皂苷(PNS)对脑缺血大鼠的神经保护作用。方法:将96只Wistar大鼠随机均分为假手术(Sham)组、大脑中动脉闭塞(MCAO)组和MCAO+PNS组(腹腔注射PNS 100 mg/kg)。利用神经功能缺陷评分和平衡木实验评估大鼠神经和运动功能。利用2,3,5-三苯基氯化四氮唑(TTC)染色检测脑梗死体积。利用苏木素-伊红染色和尼氏染色观察海马组织的病理变化。利用免疫组织化学染色测定各组大鼠大脑皮质中Beclin-1与微管相关蛋白1轻链3-II(LC3-Ⅱ)的水平。利用Western blot测定脑组织中Beclin-1、LC3-Ⅱ与单磷酸腺苷活化蛋白激酶(AMPK)/雷帕霉素靶蛋白(mTOR)信号通路相关因子的蛋白水平。结果:与Sham组相比,MCAO组海马组织呈现神经元坏死,胞质边界不清,萎缩严重;神经缺陷评分、横梁行走时间和脑梗死体积显著增加(P<0.05);脑组织中Beclin-1、LC3-Ⅱ蛋白表达水平,p-AMPKα/AMPKα比值及Beclin-1、LC3-Ⅱ阳性细胞数显著增加,p-mTOR/mTOR比值显著降低(P<0.05)。经PNS治疗后上述现象均得到明显改善。结论:PNS通过抑制AMPK/mTOR介导的自噬改善MCAO大鼠的神经功能,是治疗脑缺血的潜在有效药物。
Objective:To explore the neuroprotective effects of Panax notoginseng saponin(PNS)on rats with cerebral ischemia.Method:Ninety-six Wistar rats were randomly divided into Sham operation(Sham)group,middle cerebral artery occlusion(MCAO)group and MCAO+PNS group(intraperitoneal injection of PNS 100 mg/kg).Neurological function deficit score and balance beam test were used to evaluate neural and motor function in rats.2,3,5-triphenyl tetrazolium chloride(TTC)staining was used to detect the volume of cerebral infarction.Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of hippocampal tissue.Levels of Beclin-1 and LC3-Ⅱ in the cerebral cortex of the rats were measured by immunohistochemical staining.The protein levels of Beclin-1,microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)and AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway related factors in brain tissue were determined by Western blot.Results:Compared with Sham group,MCAO group showed neuronal necrosis,unclear cytoplasmic boundary and severe atrophy in the hippocampal tissue;Neurological deficit score,cross beam walking time and cerebral infarction volume were significantly increased(P<0.05);Beclin-1 and LC3-Ⅱ protein expression levels,p-AMPKα/AMPKαratio and the number of Beclin-1 and LC3-Ⅱ positive cells in brain tissue were significantly increased,while p-mTOR/mTOR ratio were significantly decreased(P<0.05).After PNS treatment,the above phenomena were significantly improved.Conclusion:PNS can improve the neurological function of MCAO rats by inhibiting AMPK/mTOR pathway mediated autophagy,which is a potential effective drug for the treatment of cerebral ischemia.
作者
张露
颜丽君
ZHNAG Lu;YAN Lijun(Training Center of Chongqing Medical College,Chongqing 400030,China)
出处
《神经解剖学杂志》
北大核心
2025年第3期298-304,共7页
Chinese Journal of Neuroanatomy
基金
重庆市基础与前沿研究计划项目(Y2022013573)。
