摘要
目的探究中药复方开心散调控中枢神经炎症系统抗抑郁的作用机制。方法制备开心散不同配伍比例提取物,采用小鼠慢性应激压力(CUMS)模型,通过糖水偏嗜实验、悬尾实验和强迫游泳实验评价开心散不同配伍比例的抗抑郁功效。采用ELISA法测定受试动物海马组织促炎物质如脂多糖(LPS)、IL-1β、IL-6、TNF-α的含量。采用免疫组织化学染色法观察受试动物海马区小胶质细胞形态。进而采用LPS促进小鼠小胶质永生化细胞(BV2)炎性因子表达细胞模型,采用ELISA法评价开心散抑制炎症因子表达的作用,采用Western blotting法考察NF-κB信号通路的调控情况。结果开心散不同配伍比例能显著上调模型小鼠糖水偏嗜率,缩短小鼠悬尾和强迫游泳不动时间,以D-652效用最强。该配伍比例通过抑制NF-κB的入核和抑制NF-κB磷酸化等环节,下调BV2细胞中炎症因子IL-1β、IL-6、TNF-α的表达水平。结论对中枢神经炎症的调控是中药复方开心散抗抑郁的重要作用环节。
Objective To explore the anti-depression mechanism of Kai-Xin-San via regulation of inflammation cytokine levels in hippocampus of depression-like mice. Methods The extracts of Kai-Xin-San(KXS) were prepared with different compatible ratios were prepared and the anti-depression effects of Kai-Xin-San were evaluated by behavioral tests on chronic expected mild stress(CUMS) induced depression-like mice. Amounts of LPS, IL-1β, IL-6 and TNF-α in hippocampus were determined by ELISA tests. Morphology of microglia was observed by immunohistochemistry methods in hippocampus. BV2 mouse microglia cell line was used to evaluate the effect of KaiXin-San on decreasing the expression of inflammatory cytokines. In addition, effects of KXS on regulating NF-κB signaling pathway were explored by Western blotting. Result Kai-Xin-San significantly ameliorated the depressionlike behaviors in presence of increased sucrose preference rate and decreased immobile time of tail suspension and forced swimming. D-652 ratio showed comparative better effect in behavior tests and decreasing the expressions of inflammatory cytokines such as IL-1β, IL-6 and TNF-α in hippocampus. On BV2 cells, KXS also decreasing expressions of inflammatory cytokines by inhibiting NF-κB entering into nuclear and suppressing the phosphorylation of NF-κB. Conclusions Regulation of inflammation cytokines in hippocampus accounted for KXS exerting antidepression effect on CUMS induced depression-like mice.
作者
曲苏晨
曹程
戚明珠
刘梦秋
段金廒
朱悦
Qu Suchen;Cao Cheng;Qi Mingzhu;Liu Mengqiu;Duan Jinao;Zhu Yue(School of Pharmacy,Key Laboratory for Modern Research of Traditional Chinese Medicine of Jiangsu,Jiangsu Key Laboratory for High Technology Research of TCM Formulae,Nation and local union project research center of Chinese Medicinal Resources Industrialization and Innovative drug from TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing University of Chinese Medicine,Nanjing,210023,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2019年第11期2302-2309,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会面上项目(81673720):基于压力应激-肠道微生态-中枢神经炎症系统调节的开心散抗抑郁作用机制研究
负责人:朱悦
江苏省方剂高技术研究重点实验室开放课题(FJGJS-2015-10):抗抑郁六类中药新药加味开心散的成药性研究
负责人:朱悦,詹华强
江苏省研究生科研与实践创新计划(KYCX18-1612):开心散调控压力应激-肠道微生态-中枢神经炎症系统抗抑郁机制研究,负责人:曹程。
关键词
开心散
神经炎症
抑郁症
Kai-Xin-San
neuronal inflammation
depression
