小补心汤总黄酮对获得性无助小鼠的抗抑郁作用及其对HPA轴功能的影响  

Total flavonoids extracted from xiaobuxin-tang on hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model

作　　者：陈力[1,2] 薛瑞[2] 于能江 王玉露[2] 胡晓旭[2] 仇志坤[1,2] 赵楠[2] 李云峰[2] 徐江平[1] 张有志[2] 

机构地区：[1]南方医科大学药学院药理学系,广东广州510515 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药理学通报》2015年第6期815-821,共7页Chinese Pharmacological Bulletin

基　　金：国家科技重大专项新药创制专项(No 2012ZX09102101-004);国家自然科学基金资助项目(No 81302761;81274117;30973516)

摘　　要：目的采用小鼠获得性无助模型评价小补心汤总黄酮(XBXT-2)的抗抑郁作用,并探究在应激状态下,XBXT-2对下丘脑-垂体-肾上腺轴(HPA)功能的调节作用。方法采用电脑程序控制的穿梭箱条件反射系统,给予不可逃避的足底电击诱导获得性无助模型,经过穿梭箱回避程序筛选,将成功诱导无助行为的小鼠分为模型组、度洛西汀(Dlx,20mg·kg-1)组和XBXT-2(25,50 mg·kg-1)组,灌胃给药4 d,每日采用条件性回避反应测试程序,测定小鼠的逃避失败次数和逃避潜伏期。行为学检测结束后,采用酶联免疫吸附试验法检测血清皮质酮(CORT)和促肾上腺皮质激素(ACTH)水平、蛋白印迹法检测海马糖皮质激素受体(GRα/β)蛋白和脑源性神经营养因子(BDNF)的表达水平。结果亚慢性给予XBXT-2(25,50 mg·kg-1)可明显减少获得性无助小鼠逃避失败次数和(或)逃避失败潜伏期,在行为学有效基础上,亦可明显降低获得性无助小鼠血清CORT和ACTH水平,上调海马GRα/β蛋白和BDNF的表达。结论 XBTX-2在小鼠获得性无助模型中具有抗抑郁作用,作用机制可能与其抑制HPA轴功能亢进有关。Aim To investigate the effect of the total flaconoids extracted from Xiaobuxin-Tan g （ XBXT-2 ） on the hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model. Methods Learned helplessness was induced by inescapable foot shock stress over 1h session for 5 days. After screen-ing, we divided learned helplessness mice into five groups：IS, inescapable shock;Dlx, dulxetine（20 mg ·kg^-1）;XBXT-2（25,50 mg·kg^-1）. Latency to es-cape shocks and escape failure had been recorded. During the test, Dlx（20 mg·kg^-1 ） and XBXT-2（25, 50 mg·kg^-1 ） were administered intragastrically once daily for four days. Serum corticosterone level and ad-renocorticotropic hormone （ ACTH ） level were meas-ured by ELISA, and expression of glucocorticoids re-ceptor （ GR） α/β and brain-derived neurotrophic fac-tor （ BDNF ） in hippocampus was determined using Western blot method. Results XBXT-2 （25,50 mg· kg^-1 ） or duloxetine treatment showed antidepressant effect in mouse learned helplessness model, as demon-strated by the decreased escape failure and escape la-tency. Our ELISA results showed that XBXT-2 or du-loxetine significantly decreased serum corticosterone level and its upstream stress hormone ACTH level in learned helplessness mice. Furthermore, Western blot result demonstrated XBXT-2 treatment increased GRs and BDNF expression in hippocampus. Conclusions XBXT-2 produces significant antidepressant effect on learned helplessness mice. In addition, the modulation of HPA axis produced by XBXT-2 may be important mechanism underlying its antidepressant-like effect in mouse learned helplessness model.

关 键 词：小补心汤总黄酮 抗抑郁 获得性无助模型 行为 HPA轴 脑源性神经营养因子 

分 类 号：R-332[医药卫生] R256.2