基于MEK/ERK通路探讨柴胡加龙骨牡蛎汤治疗失眠大鼠的机制  

Analysis on Mechanisms of Chaihu Jia Longgu Muli Decoction in the Treatment of Insomnia Rats Based on MEK/ERK Pathway

作　　者：金翔[1] 张微[1] 张德新[1] 梅群丽[1] 宋祖琪[1] 段绮云[1] 马彪[1] 刘智宇[1] Jin Xiang;Zhang Wei;Zhang Dexin;Mei Qunli;Song Zuqi;Duan Qiyun;Ma Biao;Liu Zhiyü(Department of Encephalopathy,Traditional Chinese Medicine Hospital of Three Gorges University(Yichang Traditional Chinese Medicine Hospital),Yichang 443001)

机构地区：[1]三峡大学中医医院(宜昌市中医医院)脑病科,宜昌443001

出　　处：《中药药理与临床》2020年第1期51-54,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：湖北省卫生和计划生育委员会科研项目(编号:WJ2018M043)。

摘　　要：目的:基于细胞外调节蛋白激酶(MEK)/细胞外活化蛋白激酶(ERK)通路探讨柴胡加龙骨牡蛎汤治疗失眠大鼠的机制。方法:将SD大鼠随机分为正常对照组、模型对照组、柴胡加龙骨牡蛎汤1 g/kg、1. 5 g/kg、3 g/kg组、艾司唑仑0. 1 mg/kg组,除正常对照组外,其余各组建立失眠大鼠模型,灌胃给予相应药物或生理盐水14 d,检测各组大鼠睡眠时相、记忆力的变化;以酶联免疫吸附法(ELISA)检测各组大鼠脑组织多巴胺(DA)、5-羟色胺(5-HT)含量;检测脑组织SOD、MDA水平;采用蛋白免疫印迹法检测MEK/ERK通路蛋白的表达。结果:与正常对照组相比,模型对照组大鼠睡眠时相中慢波睡眠浅睡期(SWS1)、慢波睡眠深睡期(SWS2)及快速眼球运动睡眠(REMS)持续时间、大鼠脑组织中5-HT、SOD含量均明显下降,大鼠找到平台时间、脑组织中DA及MDA含量、p-MEK/MEK、p-ERK/ERK比值明显升高(P <0. 05);与模型对照组相比,柴胡加龙骨牡蛎汤三个剂量组及艾司唑仑0. 1 mg/kg组大鼠睡眠时相中SWS1、SWS2及REMS持续时间、大鼠脑组织中5-HT、SOD含量均明显升高,大鼠找到平台时间、大鼠脑组织中DA及MDA含量、p-ERK/MEK、p-ERK/ERK比值均明显下降(P <0. 05),且柴胡加龙骨牡蛎汤作用呈剂量依赖性;柴胡加龙骨牡蛎汤3 g/kg组与艾司唑仑组作用相比无差异。结论:柴胡加龙骨牡蛎汤可能通过抑制MEK/ERK通路激活治疗大鼠失眠。Objective: To explore the mechanism of Chaihu Jia Longgu Muli Decoction in treating insomnia rats based on MEK/ERK pathway.Methods: SD rats were randomly divided into the control group,the model group,Chaihu Jia Longgu Muli Decoction groups( 1 g/kg,1. 5 g/kg,3 g/kg) and 0. 1 mg/kg estazolam group. Insomnia rat models were established in all groups except the control group. All rats were administered with corresponding drugs or saline water for 14 days. After treatment,the changes of sleep phase and memory in each group were detected,the contents of dopamine( DA) and serotonin( 5-HT) in brain tissues were detected by ELISA,the levels of SOD and MDA in brain tissues were detected,and the expression of MEK/ERK pathway protein was detected by Western blotting. Results: Compared with the control group,the durations of SWS1,SWS2 and REMS,the contents of 5-HT and SOD in brain tissues of the model group were significantly decreased,while the time of finding plateau,the contents of DA and MDA,p-MEK/MEK,p-ERK/ERK ratio in brain tissues of the rats were increased. Compared with the model group,the durations of SWS1,SWS2 and REMS,the contents of 5-HT and SOD in brain tissues of rats in Chaihu Jia Longgu Muli Decoction groups( all doses) and eszolam groups were increased,while the time of finding plateau,the contents of DA and MDA contents,p-MEK/MEK,p-ERK/ERK ratio in brain tissues of the rats were decreased,and there was a dose-dependent relationship among different doses of Chaihu Jia Longgu Muli Decoction groups. There was no significant difference between 3 g/kg Chaihu Jia Longgu Muli Decoction and the estazolam group. Conclusions: Chaihu Jia Longgu Muli Decoction has the effect on insomnia in rats by inhibiting MEK/ERK activation.

关 键 词：柴胡加龙骨牡蛎汤 细胞外调节蛋白激酶/细胞外活化蛋白激酶通路 失眠大鼠 分子机制 

分 类 号：R285.5[医药卫生—中药学]