摘要
目的:观察苦参碱(Matrine)对缺血性脑中风小鼠的神经保护作用及对缺氧缺糖诱导的神经元和星形胶质细胞损伤的减轻作用,并初步探讨可能的作用机制。方法:采用原代培养小鼠大脑皮层神经元及星形胶质细胞缺氧缺糖模型(Oxy-gen and glucose deprivation,OGD),MTT法和测定乳酸脱氢酶(LDH)观察Matrine对OGD神经元及星形胶质细胞的损伤是否有减轻作用;建立小鼠永久性大脑中动脉阻塞(Permanent mid-dle cerebral artery occlusion,pMCAO)模型,观察Matrine 10min、1h、3h及6h四个不同时间点给药后,脑梗死面积和神经症状的改善情况及其分子机制是否与抑制神经元及星形胶质细胞NF-κB信号通路有关。结果:经OGD诱导后,原代培养小鼠大脑皮层神经元及星形胶质细胞活力明显下降,与OGD模型组比较,给予Matrine(50μmol/L)干预后,神经元及星形胶质细胞的存活率明显提高(P<0.01);与此同时,OGD可使小鼠大脑皮层星形胶质细胞LDH漏出量增高(P<0.01),Matrine(50μmol/L)与模型组比较,LDH漏出量明显降低(P<0.01);Matrine(37.5mg/kg)10min、1h两个给药时间点的脑梗死面积与模型组比较明显减少(P<0.01);与模型组比较,Martine 10min、1h两个给药时间点术后24h的神经症状评分明显降低(P<0.01);Matrine可降低pMCAO缺血区IκBα与IKK蛋白的表达水平(P<0.01,P<0.05),同时降低细胞核NF-κB蛋白的表达(P<0.01)。结论:Matrine可通过直接保护神经元及星形胶质细胞改善缺血性脑中风症状,其作用时间窗可能在发病1h以内,Matrine保护作用可能与NF-κB信号通路有关。
AIM： To investigate the protective effects of matrine on neurons and astrocytes in focal ischemia induced by permanent middle cerebral artery occlusion（pMCAO） in mouse and explore the possible mechanism.METHODS： MTT and LDH assays were used to assess the protective effects of matrine in primary culture of neurons and astrocytes injured by oxygen and glucose deprivation（OGD）.The improvement effects of matrine in 10 min,1 h,3 h and 6 h on focal ischemia induced by pMCAO in mouse were evaluated by neuroethology and staining images.The expression of IκBα,IKK,p-IKK and NF-κB in ischemic region 24 h after pMCAO were evaluated by Western blot.RESULTS：Matrine at 50 μmol/L increased the survival rates of neurons and astrocytes and decreased the LDH leakage in astrocytes injured by OGD.In intact animals,matrine（37.5 mg/kg） improved the neuroethology of pMCAO mouse,the time window may be within 1 h after onset of the ischemia;matrine（37.5 mg/kg） significantly reduce infarction volumes of pMCAO mouse and the expression of IκBα,IKK and NF-κB in ischemic area.CONCLUSION： The present findings suggest that matrine,administrated 1 h after ischemia,has protective effects on neurons and astrocytes,possibly via inhibition of NF-κB signaling pathway.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2012年第12期1343-1348,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
浙江省自然科学基金项目(Y2111133)
