异鼠李素激活PI3K/Akt/GSK-3β/CREB信号通路减轻鱼藤酮诱导的PC12细胞损伤  

Isorhamnetin prevents PC12 cell from rotenone-induced injury via PI3K/Akt/GSK-3β/CREB signaling pathway

作　　者：谭会洁 宋俊科 石峰 张雯 杜冠华 郭常川 TAN Hui-jie;SONG Jun-ke;SHI Feng;ZHANG Wen;DU Guan-hua;GUO Chang-chuan(Shandong Institute for Food and Drug Control,Jinan 250101,China;State Key Lab of Bioactive Substances and Functions of Natural Medicines,Beijing Key Lab of Drug Target and Screening Research,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]山东省食品药品检验研究院,济南250101 [2]中国医学科学院&北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,药物靶点研究与新药筛选北京市重点实验室,北京100050

出　　处：《中国药理学通报》2020年第2期272-276,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81573606)。

摘　　要：目的探讨异鼠李素(isorhamnetin,ISO)是否能够通过激活PI3K/Akt/GSK-3β/CREB通路减轻鱼藤酮对PC12细胞的损伤作用。方法采用MTT法检测细胞活力,LDH检测乳酸脱氢酶释放,Western blot法测定p-Akt、Akt、p-GSK-3β、GSK-3β、p-CREB和CREB蛋白表达。结果与对照组相比,鱼藤酮损伤后PC12细胞活力明显降低,CREB的磷酸化程度显著降低。异鼠李素预处理组细胞存活率和磷酸化CREB的表达均高于鱼藤酮损伤模型组。此外,异鼠李素预处理增强了鱼藤酮损伤后PC12细胞中Akt和GSK-3β的磷酸化程度。加入PI3K抑制剂LY294002可以抑制Akt、GSK-3β和CREB的磷酸化水平,从而部分消除异鼠李素对鱼藤酮损伤PC12细胞的神经保护作用。结论异鼠李素可能通过PI3K/Akt/GSK-3β/CREB信号通路发挥PC12细胞保护作用。Aim To investigate whether isorhamnetin could protect against rotenone-induced PC12 cells injury via regulating PI3K/Akt/GSK-3β/CREB pathway.Methods PC12 cell viability was determined by MTT and LDH assays.The expressions of Akt,p-Akt,GSK-3β,p-GSK-3β,CREB and p-CREB were measured by Western blot.Results The cell viability and level of phospho-CREB significantly decreased in PC12 cells exposed to rotenone when compared to control group.Both the cell viability and the expression of phospho-CREB in cells pretreated with isorhamnetin were higher than those of cells exposed to rotenone alone.Moreover,pretreatment of PC12 cells with isorhamnetin enhanced phosphorylation of Akt and GSK-3β.The addition of LY294002 could suppress the phosphorylation of Akt,GSK-3βand CREB,resulting in abolishment of neuroprotective effects of isorhamnetin on cells exposed to rotenone.Conclusion Isorhamnetin might alleviate rotenone-induced PC12 cells injury partially via the PI3K/Akt/GSK-3β/CREB signaling pathway.

关 键 词：异鼠李素 鱼藤酮 蛋白激酶B 糖原合成酶激酶-3 环腺苷酸反应结合蛋白 神经保护 

分 类 号：R284.1[医药卫生—中药学] R329.25[医药卫生—中医学]