补阳还五汤介导Cav1调控Notch信号通路对脑缺血后星形胶质细胞转分化的影响  

Effects of Buyang Huanwu Decoction mediated Cav1 in regulation of Notch signaling pathway on astrocyte transdifferentiation after cerebral ischemia

作　　者：欧阳银 陈博威 曾繁佐 刘英飞 田丰铭 徐雅倩 易健[2] 刘柏炎[1,2,3] OUYANG Yin;CHEN Bowei;ZENG Fanzuo;LIU Yingfei;TIAN Fengming;XU Yaqian;YI Jian;LIU Baiyan(The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Academy of Chinese Medicine,Changsha 410006,China)

机构地区：[1]湖南中医药大学第一附属医院,长沙410007 [2]湖南中医药大学,长沙410208 [3]湖南省中医药研究院,长沙410006

出　　处：《中华中医药杂志》2024年第8期3937-3942,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82074251);湖南省自然科学基金项目(No.2022JJ30357);湖南省研究生创新课题(No.CX20230808,No.CX20220805,No.CX20220815)。

摘　　要：目的:基于小窝蛋白1(Cav1)/Notch信号通路探讨补阳还五汤对脑缺血后星形胶质细胞转分化的作用机制。方法:将野生(WT)小鼠及Cav1^(-/-)(KO)小鼠随机各分为假手术(Sham)组、模型(Model)组和补阳还五汤(BHD)组,造模前7天予以脑内注射GFAP-EGFP腺相关病毒,采用大脑中动脉栓塞法(MCAO)造模后给予药物干预21 d后评估补阳还五汤疗效,观察缺血侧皮质区星形胶质细胞转分化情况,检测缺血侧皮质区Notch信号通路蛋白表达。结果:与同基因型Sham组比较,Model组神经功能缺损评分显著升高、病理损伤明显,NeuN表达显著降低(P<0.01,P<0.05);与同基因型Model组比较,BHD组神经功能缺损评分降低,改善缺血侧皮质病理损伤,NeuN表达显著升高,EGFP-NeuN共定位显著增强,Notch1、Hes1以及DLL1蛋白水平显著降低(P<0.01,P<0.05);与WT-Model组比较,KO-Model组神经功能缺损评分升高,缺血侧皮质损伤加重,NeuN表达显著降低,Hes1蛋白表达显著升高(P<0.05);与WT-BHD组比较,KO-BHD组神经功能缺损评分显著升高,缺血侧皮质损伤加重,EGFP-NeuN共定位减弱,Notch1蛋白表达显著升高(P<0.05)。结论:补阳还五汤能够促进脑缺血后星形胶质细胞向神经元转分化,其作用机制可能与通过介导Cav1调控Notch信号通路有关。Objective:To investigate the mechanism of Buyang Huanwu Decoction on astrocyte transdifferentiation after cerebral ischemia based on caveolin-1(Cav1)/Notch signaling pathway.Methods:Wild(WT)mice and Cav1^(-/-)(KO) mice were randomly divided into sham group,model group and Buyang Huanwu Decoction(BHD)group.Seven days before modeling,GFAP-EGFP adeno-associated virus was injected into the brain,MCAO method was used to create a model,and drug intervention was given for 21 days.The transdifferentiation of astrocytes in the cortical area of the ischemic side was observed,and the ischemic side was detected.Notch signaling pathway protein expression in cortical area.Results:Compared with the Sham group of the same genotype,the neurological deficit score of the model group was significantly increased,the pathological damage was obvious,and the expression of NeuN was significantly decreased(P<0.01,P<0.05).Compared with the model group of the same genotype,the neurological deficit score of the BHD group was significantly reduced,the pathological damage of the ischemic cortex was significantly improved,the expression of NeuN was significantly increased,the colocalization of EGFP-NeuN was significantly enhanced,and the levels of Notch1,Hes1 and DLL1 proteins were significantly decreased(P<0.01,P<0.05).Compared with the WT-Model group,the neurological deficit score of the KO-Model group was significantly increased,the injury of the ischemic cortex was significantly aggravated,the expression of NeuN protein was significantly decreased,the expression of Hesl protein was significantly increased(P<0.05).Compared with the WT-BHD group,the neurological deficit score of the KO-BHD group was significantly increased,the injury of the ischemic cortex was significantly aggravated,the co-localization of EGFP-NeuN was weakened,and the expression of Notchl protein was significantly increased(P<0.05).Conclusion:Buyang Huanwu Decoction can promote the transfer of astrocytes to nerve cells after cerebral ischemia,and its mechanism may be relat

关 键 词：补阳还五汤 脑缺血 星形胶质细胞 转分化 小窝蛋白1 NOTCH信号通路 

分 类 号：R285[医药卫生—中药学]