摘要
目的古代文献记载小补心汤(XBXT,由代赭石、旋覆花、竹叶和淡豆豉4味中药组成)有缓解抑郁情绪的作用。应用大鼠慢性应激模型探讨XBXT总黄酮(XBXT-2)的抗抑郁作用及可能机制。方法连续28d给予大鼠一系列慢性不可预测性的刺激建立慢性应激模型,同时给予XBXT-2(25或50mg·kg-1·d-1,ig)或丙米嗪(10mg·kg-1·d-1,ig),采用蔗糖饮水实验、开场活动实验和新奇抑制摄食实验观察抗抑郁行为效应;采用酶联免疫吸附实验检测血清皮质酮含量,Western蛋白印迹法检测海马糖皮质激素受体(GR)α/β、脑源性神经营养因子(BDNF)、磷酸化cAMP反应元件结合蛋白(p-CREB)、细胞外信号调节激酶(ERK1/2)及其磷酸化形式(p-ERK1/2)蛋白表达水平。结果XBXT-2或丙米嗪可逆转慢性应激大鼠蔗糖饮水偏嗜度降低、自发活动减少及新奇抑制摄食潜伏期延长,显著降低应激大鼠血清皮质酮含量,上调海马GRα/β,BDNF,p-CREB和p-ERK1/2蛋白表达。结论XBXT-2对慢性应激大鼠具有抗抑郁作用,其机制可能与抑制下丘脑-垂体-肾上腺轴的过度激活,上调海马BDNF相关的神经营养通路中蛋白表达有关。
AIM It was recorded that Xiaobuxin-Tang （ XBXT ）, comprising of Haematitum, Flos Inulae, Folium Phyllostachydis Nigrae var. Henonis and Semen Sojae Praeparatum, could alleviate depressive disorders. The aim of present study is to explore further antidepressant effect of the total flavonoids extracted from XBXT （XBXT-2） and its possible mechanisms. METHODS Rats were exposed to chronic mild stress （CMS） for 28 consecutive days with coadministration of XBXT-2 （25, 50 mg·kg^-1·d^-1,ig） or imipramine （IMI, 10mg·kg^-1·d^-1,ig）. Sucorse preference test, open field test and novelty-sup- pressed feeding test were applied to assess the behavioral efficacy; serum corticosterone level was measured by ELISA; hippocampal glucocorticoids receptor （GR） α/β, brain-derived neurotrophic factor （BDNF） , phosphor-cAMP response element binding protein （p-CREB） , extracellular signal regulated kinase （ERK1/ 2） and phosphor-extracellular signal regulated kinase （p-ERK1/2） expression were tested using Western blot. RESULTS XBXT-2 or IMI treatment reversed depression-like behaviors such as reduced sucrose preference, deficient locomotory activity, prolonged latency to novelty-suppressed feeding in CMS rats. In addition, XBXT-2 or IMI significantly decreased concentration of serum corticosterone and increased expressions of hippocampal GR α/β, BDNF, p-CREB, ERK1/2 and p-ERK1/2 in CMS rats. CONCLUSION XBXT-2 produces significant antidepressant effect on CMS model rats, which may be related to its functional regulation of hypothalamic pituitary adrenal axis and up-regulation of BDNF-related neurotrophic signal pathway within hippocampus.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2008年第2期102-107,共6页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金面上项目(30400600)
国家自然科学基金面上项目(30472018)
国家重点基础研究发展计划(2007CB512307)
国家高技术研究发展计划(2007AA02Z400)~~
关键词
小补心汤
黄酮类
抗抑郁药
行为
动物
Xiaobuxin-Tang
flavonoids
anti- depressive agents
behavior, animal
