复方柴金解郁片对抑郁症失眠大鼠脑内GABA受体表达的影响  

Effects of compound Chaijin Jieyu tablets on expressionof GABA receptor in brain regions of depressive insomnia rats

作　　者：刘灿[1] 黄会珍 赵洪庆[1] 邹蔓姝 王叶情 李春艳 王宇红[1] 李强翔 LIU Can;HUANG Hui-zhen;ZHAO Hong-qing;ZOU Man-shu;WANG Ye-qing;LI Chun-yan;WANG Yu-hong;LI Qiang-xiang(Hunan University of Chinese Medicine,National Key Lab Breeding Base of Chinese Medicine Powder and Innovative Medicine/Technology Innovation Center,Changsha 410208,China;Ningxia Medical University Affiliated People′s Hospital of Ningxia Hui Autonomous Region,Yinchuan 750001,China)

机构地区：[1]湖南中医药大学,中药粉体与创新药物国家重点实验室培育基地/科技创新中心,湖南长沙410208 [2]宁夏医科大学附属人民医院,宁夏银川750001

出　　处：《中国药理学通报》2021年第5期724-730,共7页Chinese Pharmacological Bulletin

基　　金：国家重大新药创制(No 2017ZX09309026);国家自然科学基金面上项目(No 81874464);湖南省科技厅重点研发项目(No 2018DK2014);湖南省教育厅科学研究项目(No 19C1437)。

摘　　要：目的探究复方柴金解郁片对抑郁症失眠大鼠脑内GABA受体表达的影响。方法SD大鼠随机分为空白组、模型组、阳性药(盐酸文拉法辛13.5 mg·kg^(-1)+地西泮0.9 mg·kg^(-1))组、复方柴金解郁片高(10.8 g·kg^(-1))、中(5.4 g·kg^(-1))、低(2.7 g·kg^(-1))剂量组。除空白组外,各组均采用慢性不可预见性轻度应激联合慢性睡眠剥夺的方法制作抑郁症失眠大鼠模型。旷场实验和糖水偏好实验检测大鼠抑郁样行为;翻正反射检测睡眠行为;ELISA检测海马和下丘脑Glu和GABA含量;qRT-PCR和Western blot检测GAD67、GABA AR、GABA BR mRNA及蛋白表达。结果与模型组相比,各复方柴金解郁片给药组活动次数和糖水偏嗜度增加;睡眠潜伏期缩短,睡眠时间延长,入睡率增加;Glu含量减少、GABA含量增加;GAD67、GABA AR、GABA BR的蛋白及基因表达增加。结论复方柴金解郁片具有良好的抗抑郁症失眠功效,其机制可能与增加脑内GABA受体表达有关。Aim To explore compound Chaijin Jieyu tablets on expression of GABA receptor in brain regions of depressive insomnia rats.Methods Seventy-two male SD rats were randomly divided into control,model,positive drug(venlafaxine hydrochloride13.5 mg·kg^(-1)+diazepam 0.9 mg·kg^(-1)),high(10.8 g·kg^(-1)),medium(5.4 g·kg^(-1))and low(2.7 g·kg^(-1))dose of compound Chaijin Jieyu tablets group.Except control,chronic unpredictable mild stress with chronic sleep deprivation was used to build the model of depressive insomnia rats.The behavioral changes of rats were detected by open field test,sucrose preference test and righting reflex test.The contents of Glu and GABA in hippocampus and hypothalamus of rats were detected by ELISA.The protein expression levels of GAD67,GABA AR and GABA BR in hippocampus and hypothalamus of rats were detected by Western blot.The GAD67,GABA AR and GABA BR mRNA expression in hippocampus and hypothalamus of rats were detected by qRT-PCR.Results Compared with model group,the number of activities and sucrose water preference were improved by compound Chaijin Jieyu tablets;the incubation period of fallen asleep was shortened,and the sleep duration was extended,and the increase of sleep rate was caused by subthreshold dose of pentobarbital sodium.Furthermore,Glu and GABA content increased in compound Chaijin Jieyu tablets groups compared with model group;the relative expression levels of GAD67,GABA AR,GABA BR protein and gene decreased.Conclusions Compound Chaijin Jieyu tablets could develop anti-depressive insomnia effect,and its mechanism may be related to the increase of GABA receptor expression in hippocampus and hypothalamus.

关 键 词：复方柴金解郁片 抑郁症失眠 海马 下丘脑 GABA AR GABA BR 

分 类 号：R-332[医药卫生] R285.5