基于Notch信号通路探讨栝楼桂枝颗粒对脂多糖活化小胶质细胞诱导神经元损伤的保护作用  

The protective effect of Gualou Guizhi granules on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway

作　　者：李雪珍 邹小雪 陈雯婷 冯怡 李亚男 张玉琴[1] 南丽红[1] LI Xue-zhen;ZOU Xiao-xue;CHEN Wen-ting;FENG Yi;LI Ya-nan;ZHANG Yu-qin;NAN Li-hong(Pharmacy College of Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122

出　　处：《中国药理学通报》2025年第4期781-786,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.81803768);福建省自然科学基金资助项目(No.2024J01127);福建中医药大学基础类学科科研提升计划项目(No.XJC2023013)。

摘　　要：目的基于Notch信号通路探讨栝楼桂枝颗粒(Gualou Guizhi granule,GLGZG)对脂多糖活化小胶质细胞后诱导神经元损伤的保护作用。方法脂多糖激活的小胶质细胞(BV2)与神经元共培养构建神经元损伤模型,将细胞分为正常对照组、模型组、Notch抑制剂(DAPT)组、GLGZG(50、100、200 mg·L^(-1))组、DAPT+100 mg·L^(-1)GLGZG组。干预后,CCK-8法检测HT22细胞活性,real-time PCR检测相关mRNA表达,Western blot检测相关蛋白表达。结果与模型组比,GLGZG干预后细胞活性明显提高,下调IL-6、IL-12、Bax、Notch1、caspase-3、Delta-1、NICD、RBPSUH、HES1等的表达,上调Bcl-2的表达(P<0.05)。与模型组比,经DAPT分别作用后,NICD、RBPSUH、HES1 mRNA和蛋白的表达明显降低(P<0.05),且与GLGZG无叠加作用。结论GLGZG可能通过抑制炎症因子与细胞凋亡,抑制Notch信号通路,从而发挥神经保护作用。Aim To investigate the protective effect of Gualou Guizhi granules(GLGZG)on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway.Methods LPS-activated microglia were co-cultured with neurons to construct neuron injury models,and the cells were divided into the control group,model group,Notch inhibitor(DAPT)group,GLGZG(50,100,200 mg·L^(-1))group,DAPT+100 mg·L^(-1) GLGZG group.After intervention,the activity of HT22 cells was detected by CCK-8 method,and relative mRNA expression was detected by real-time PCR.The relative protein expression was detected by Western blot.Results Compared with the model group,after GLGZG intervention,the cell activity was significantly improved,GLGZG decreased IL-6,IL-12,Bax,Notch1,caspase-3,Delta-1,NICD,RBPSUH,HES1 expression,and increased Bcl-2 expression(P<0.05).Compared with the model group,the NICD,RBPSUH and HES1 mRNA and protein expressions significantly decreased after DAPT treatment(P<0.05),and there was No.superposition effect with GLGZG.Conclusion GLGZG may play a neuroprotective role by inhibiting inflammatory factors and apoptosis,and inhibiting Notch signaling pathway.

关 键 词：栝楼桂枝颗粒 脂多糖 小胶质细胞 NOTCH信号通路 神经炎症 HT22细胞 

分 类 号：R-332[医药卫生] R282.71R322.8R641R977.6