基于线粒体融合分裂探究山茱萸及Cornuofficinaliside G对Aβ_(25-35)诱导AD小鼠神经元突触损伤的影响

Exploration on the effects of Corni Fructus and Cornuofficinaliside G on synaptic damage in Aβ25-35-induced AD mice based on mitochondrial fusion and fission

目的:探究山茱萸及化合物Cornuofficinaliside G(CorG)对β淀粉样蛋白片段25-35(Aβ_(25-35))见图18。诱导阿尔茨海默症(AD)的干预作用。方法:MTT法检测不同浓度山茱萸提取物和化合物CorG对Aβ_(25-35)诱导PC12细胞损伤的影响;体外实验选用雄性C57BL/6J小鼠,随机分为对照组、模型组、石杉碱甲组(0.2 mg/kg)、山茱萸组(2.6 g/kg)、CorG组(20 mg/kg)。除对照组采用脑部注射0.9%氯化钠溶液,其余组脑部注射Aβ_(25-35)(200μmol/L)构建AD模型;灌胃24 d后,检测行为学指标,观察小鼠海马神经元、突触和线粒体病理变化;检测脑组织氧化应激相关指标和海马突触和线粒体融合分裂相关蛋白的表达。结果:山茱萸提取物和化合物CorG能显著增加Aβ_(25-35)诱导PC12损伤细胞的细胞活力;并且山茱萸和CorG显著增加AD小鼠的认知功能;减缓神经元固缩、丢失和线粒体及突触损伤;改善氧化应激及线粒体融合分裂蛋白表达。结论:山茱萸和CorG可能通过调节线粒体融合分裂和氧化应激来改善Aβ_(25-35)诱导AD小鼠的认知功能障碍和突触损伤。

Objective:To investigate the interventional effects of Corni Fructus extract(SZY)and the compound Cornuofficinaliside G onβ-amyloid fragment 25-35(Aβ_(25-35))-induced Alzheimer’s disease(AD).Methods:The effects of different concentrations of SZY and CorG on Aβ_(25-35)-induced PC12 cell injury were examined by MTT.In vitro experiments were conducted in male C57BL/6J mice were randomly divided into control group,model group,Huperzine A group(0.2 mg/kg),SZY group(2.6 g/kg)and CorG group(20 mg/kg).The AD model was constructed by injecting Aβ_(25-35)(200μmol/L)into the brains of all groups except the control mice,which were injected with saline.After 24 days of gavage,mice were tested for behavioural indices;pathological changes in hippocampal neurons,synapses and mitochondria were observed;brain tissue oxidative stress-related indices and expression of hippocampal synaptic and mitochondrial fusion splitting-related proteins were measured.Results:SZY and CorG significantly increased cell viability in Aβ_(25-35)-induced PC12 cell injury.Moreover,SZY and CorG significantly increased cognitive function,reduced neuronal sequestration,loss and mitochondrial and synaptic damage,and improved oxidative stress and mitochondrial fusion splitting protein expression in AD mice.Conclusion:SZY and CorG ameliorat cognitive dysfunction and synaptic damage in Aβ_(25-35)-induced AD mice by regulating mitochondrial fusion and fission and oxidative stress.