氟比洛芬酯调节Akt/GSK-3β/Nrf2/HO-1信号通路改善H/R诱导的神经元损伤相关研究  

Studies on flurbiprofen exate modulating Akt/GSK-3β/Nrf2/HO-1 signaling pathways to ameliorate H/R-induced neuronal damage

作　　者：张春瑞[1] 尉建辉[2] ZHANG Chunrui;WEI Jianhui(Department of Neurology,Hanzhong People's Hospital,Hanzhong 723000,Shanxi Province,China;Department of Neurology,Baoji Central Hospital,Baoji 721000,Shanxi Province,China)

机构地区：[1]汉中市人民医院神经内科,陕西汉中723000 [2]宝鸡市中心医院神经内科,陕西宝鸡721000

出　　处：《世界临床药物》2023年第6期567-573,637,共8页World Clinical Drug

基　　金：陕西省自然科学基础研究计划(2020JM-706)。

摘　　要：目的 探究氟比洛芬酯对缺氧/复氧(hypoxia/reoxygenation,H/R)诱导的神经元损伤的影响及对有关调控机制。方法H/R诱导构建神经元损伤模型。细胞计数法检测细胞存活率;流式细胞术检测细胞凋亡率;透射电镜观察神经元损伤情况;酶联免疫吸附剂测定法检测氧化应激及炎症因子表达;蛋白质免疫印迹法检测通路蛋白水平。结果 较对照组,H/R组神经元损伤严重,神经元生存率降低[(40.51±4.03)%vs 100%],凋亡率[(66.48±6.83)%vs (1.03±0.18)%]、氧化应激及炎症反应升高,并激活Akt/GSK-3β/Nrf2/HO-1信号通路(P <0.01)。氟比洛芬酯可缓解H/R诱导的神经元损伤,升高神经元存活率[(73.36±7.08)%vs (40.51±4.03)%],降低凋亡率[(32.27±3.45)%vs (66.48±6.83)%],抑制氧化应激、炎症反应以及Akt/GSK-3β/Nrf2/HO-1信号通路(P <0.01)。结论 氟比洛芬酯可能通过促进氧化应激通路活化,保护神经元免受H/R诱导损伤。Objective To investigate the effect of flurbiprofen axetil on hypoxia/reoxygenation(H/R)-induced neuronal injury and its regulatory mechanism.Methods Neuronal injury model was induced by H/R.Cell survival rate was detected by cell counting kit-8.The apoptosis rate was detected by flow cytometry.The neuronal injury was observed by transmission electron microscopy.The expression of oxidative stress and inflammatory factors were detected by enzyme linked immunosorbent assay.The protein level of the pathway was detected by western blotting(WB).Results Compared with the control group,the neurons in the H/R group were severely damaged,the neuronal survival rate[(40.51±4.03)%vs 100%]was reduced,the apoptosis rate[(66.48±6.83)%vs(1.03±0.18)%]and the oxidative stress and inflammatory response were increased,and the Akt/GSK-3β/Nrf2/HO-1 signaling pathway was activated(P<0.01).Flurbiprofen axetil can alleviate H/R-induced neuronal injury,elevated neuronal survival rate[(73.36±7.08)%vs(40.51±4.03)%],reduce cell apoptosis rate[(32.27±3.45)%vs(66.48±6.83)%],and inhibit oxidative stress,inflammatory response and the Akt/GSK-3β/Nrf2/HO-1 signaling pathway(P<0.01).Conclusion Flurbiprofen axetil may protect neurons from H/R-induced injury by promoting the activation of oxidative stress pathway.

关 键 词：氟比洛芬酯 神经元损伤 缺氧/复氧 信号通路 

分 类 号：R96[医药卫生—药理学]