尼古丁通过PI3K/AKT信号通路上调星形胶质细胞HSF1的表达  

Nicotine Upregulates HSF1 Expression via PI3K/AKT Signaling Pathway in Astrocytes

作　　者：董智慧[1,2] 任真奎 吕菊 谢鹏 官志忠[1,2,4] 吴昌学[1,2] 禹文峰[1,2] DONG Zhihui;REN Zhenkui;LV Ju;XIE Peng;GUAN Zhizhong;WU Changxue;YU Wenfeng(Key Laboratory of Medical Molecular Biology,Guizhou Medical University,Guiyang 550004,Guizhou,China;Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education,Guizhou Medical University,Guiyang 550004,Guizhou,China;Department of Clinical Laboratory,People's Hospital,Qianxinan Buyei and Miao Autonomous Prefecture,Xingyi 562400,Guizhou,China;Department of Pathology,Guizhou Medical University,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学分子生物学重点实验室,贵州贵阳550004 [2]贵州医科大学地方病与少数民族疾病教育部重点实验室,贵州贵阳550004 [3]黔西南州人民医院检验科,贵州兴义562400 [4]贵州医科大学病理学教研室,贵州贵阳550004

出　　处：《贵州医科大学学报》2019年第3期259-263,共5页Journal of Guizhou Medical University

基　　金：国家自然科学基金(批准号:81360199);教育部科学技术研究项目(213032A);贵州省国际科技合作计划项目[黔科合外G字(2013)7026号];贵州省创新计划项目[黔教合协同创新中心(2014)06];贵州省教育厅项目(2015年贵州省普通高等学校地方病和少数民族疾病防控创新团队);贵州省教育厅项目[黔教合外G字(2013)63];贵州省科技厅计划课题[黔科合重大专项字(2014)6008]

摘　　要：目的:研究尼古丁对星形胶质细胞热休克转录因子1(HSF1)的表达的影响,并探讨其机制。方法:分离新出生24 h内乳鼠大脑皮质,进行原代培养并鉴定为星形胶质细胞,待细胞成熟后分为正常对照组、尼古丁处理组,PI3K/AKT信号通路阻断剂LY294002处理组和尼古丁+LY294002处理组,正常对照组不做任何处理;尼古丁处理组用5μmol/L尼古丁分别处理星形胶质细胞6、12、18、24 h; LY294002处理组只加10μmol/L LY294002处理;尼古丁+LY294002处理组是先加10μmol/L LY294002处理2 h后,再加入5μmol/L尼古丁共同处理18 h,免疫印迹法观察各组HSF1蛋白的表达。结果:与正常对照组相比,尼古丁处理组星形胶质细胞内HSF 1蛋白的表达上调(P <0. 05);与尼古丁处理组比较,LY294002+尼古丁处理组星形胶质细胞内HSF1表达明显受到抑制(P <0. 05)。结论:尼古丁通过PI3K/AKT信号通路上调星形胶质细胞HSF1蛋白表达。Objective:To study the effect of nicotine on the expression of heat shock transcription factor 1(HSF1)in astrocytes and explore its mechanism.Methods:To get primary rat astrocytes,the cerebral cortexes of newborn rats within 24 h were isolated,prepared for single cell suspension,cultured and verified using GFAP immunostaining.After astrocytes matured,they were divided into four groups:control group,nicotine group,LY294002(PI3K/AKT inhibitor)group and the nicotine+LY294002 group.The control group was not given any treatment,the nicotine group was treated with 5μmol/L nicotine for 6 h,12 h,18 h and 24 h,respectively;LY294002 group was given 10μmol/L LY294002;nicotine+LY294002 group was pretreated with 10μmol/L LY294002 for 2 h and then treated with 5μmol/L nicotine for 18 h.The expression levels of HSF1 protein were detected by immunoblotting.Results:Compared with the control group,HSF-1 level was upregulated in nicotine group(P<0.05).HSF1 expression level was remarkably lower in LY294002+nicotine group than that in nicotine group(P<0.01).Conclusion:Nicotine upregulates HSF1 expression through PI3K/AKT signaling pathway in astrocytes.

关 键 词：原代星形胶质细胞 热休克核转录因子1 尼古丁 PI3K/AKT信号通路 阿尔茨海默症 

分 类 号：R749.16[医药卫生—神经病学与精神病学]