解虑安神汤对焦虑小鼠脑内GABA水平及其受体表达的影响  

The GABAergic mechanism of action of Jielv Anshen Decoction in a mouse model of social isolation-induced anxiety disorders

作　　者：宋波[1] 朱功蓓 林煜涵 周宁娜[1] 

机构地区：[1]云南中医学院,昆明650500

出　　处：《中药药理与临床》2013年第6期118-121,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：云南省自然科学研究基金课题;项目编号:2008ZC098M

摘　　要：目的:通过观察解虑安神汤乙酸乙酯提取部位对社会隔离焦虑动物模型行为学及脑内-氨基丁酸(GABA)水平及其A亚型受体(GABAA-R)α1、α2、α5亚基的影响,阐明其抗焦虑的作用机制。方法:复制小鼠社会隔离焦虑模型,分为正常组(等体积溶媒)、模型组(等体积溶媒)、地西泮组(0.002g/kg)及解虑安神汤乙酸乙酯提取部位组(0.21g/kg),连续灌胃给药2周后用高架十字迷宫和旷场实验进行行为学测定;行为学实验结束后,ELISA法测定海马区GABA的含量;Western blot检测GABAA-Rα1、α2、α5亚基的蛋白表达水平。结果:模型组小鼠在开臂停留时间、OT%及进入旷场中央次数减少,海马内GABA水平下降,GABAARα1、α2亚基表达减少,GABAA-Rα5表达升高。与模型组相比,地西泮和解虑安神汤乙酸乙酯提取部位均可延长小鼠在开臂停留时间、增加OT%,并增加小鼠进入开臂次数及进入旷场中央次数,差异有显著性意义;解虑安神汤乙酸乙酯提取部位小鼠海马内GABA水平升高,GABAA-Rα1、α2亚基表达增加,GABAA-Rα5表达降低;地西泮可升高GABAA-Rα1、α2的表达,对GABA水平及GABAA-Rα5无影响。与正常对照组相比,解虑安神汤乙酸乙酯提取部位对GABAA-Rα1、α2、α5亚基表达均无明显影响;地西泮可显著升高GABAA-Rα1亚基的表达。结论:解虑安神汤乙酸乙酯提取部位可能通过增加GABA的水平、调节GABAA-R的功能发挥抗焦虑作用。Objective： By determining effects of the active compounds of Jielv Anshen decoction（J-A） on the GABA level and GABAA receptors subunites α1,α2,α5 expression in anxious animal model, to elucidate its possible mechanism of antianxiety. Methods： Socially isolated male mice were administered with J-A or Diazepam（DZP） for two weeks, then the Elevated Plus Maze Test （EPM） and Open Filed Test （OFT） was performed, and the GABA level in hippocampus was determined by ELISA; the GABAA receptors （GABAA-R）subunites α1, α2,α5 expression were detected by Western blot. Results： Compare to model group, both of J-A and DZP can attenuate anxiety-like behavior in the elevated plus maze test by increasing the open ann time, the percentage of open arm time（ OT% ） and the open arm entries in EPM, as well as increasing the entry times of central field in OFT. Compared to the model group, DZP didn＇t show any effect on GABA level and GABAA-R α5 expression, but can increase the GABAA-R α2 expression, and a marked increasing of GABAA-Rα1 even compared to the control group. J-A treatment can increase the GABA level, upregulate the expression of GABAA receptors α1, α2 subunit whereas downregulate the α5 subunite, there were no differences for the GABAA receptor α1, α2 and α5 subunits expression in J-A treated group compare to the control group. Conclusions： These data suggested that increases the reduced GABA level and normalizes the function of GABAA-R subunites α1,α2,α5 is possibly a mechanism of action for the traditional Chinese Medicine in antianxiety disorders.

关 键 词：解虑安神汤 社会隔离焦虑模型 行为学测定 GABA水平 GABAA-R表达 

分 类 号：R285[医药卫生—中药学]