麋鹿角调控慢性压力应激小鼠神经营养因子和压力应激因子抗抑郁作用研究  

Researches on Anti-depression Mechanism of Elk Antler via Regulation of Neurotrophic Factors and Stress Factors on Chronic Unpredictable Mild Stress Induced Mice

作　　者：刘梦秋[1] 曹程 曲苏晨 钱大玮[1] 段金廒[1] 朱悦[1] 赵明 Liu Mengqiu;Cao Cheng;Qu Suchen;Qian Dawei;Duan Jinao;Zhu Yue;Zhao Ming(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)

机构地区：[1]南京中医药大学药学院江苏省方剂研究重点实验室/江苏省方剂高技术研究重点实验室/中药资源产业化于方剂创新药物国家地方地方联合工程研究中心/江苏省中药资源产业化过程协同创新中心

出　　处：《世界科学技术-中医药现代化》2019年第9期1805-1812,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家科技部国家重点研发计划（2018YFC1706100）：珍稀濒危中药资源新来源的四种开发模式研究，负责人：赵明;南京中医药大学江苏省中药资源产业化过程协同创新中心重点项目（ZDXM-3-12）：麋鹿角的资源价值发现与产业化开发，负责人：朱悦;江苏省教育厅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。

摘　　要：目的考察麋鹿角提取物调控神经营养因子和压力因子抗抑郁的作用机制。方法制备麋鹿角提取物,采用小鼠慢性应激压力(chronic unpredictable mild stress,CUMS)模型,通过糖水偏嗜实验、悬尾实验和强迫游泳实验评价麋鹿角提取物的抗抑郁功效。采用ELISA法测定受试动物海马区中神经生长因子(Nerve growth factor,NGF)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的含量。采用ELISA测定受试动物血清中相应压力因子:促肾上腺皮质激素释放激素(corticotropinreleasing factor,CRF)、促肾上腺皮质激素(adreno-cortico-tropic-hormone,ACTH)、皮质醇的含量。采用大鼠星形胶质瘤细胞(C6)评价麋鹿角提取物调控神经营养因子系统的作用,并采用小鼠海马永生化细胞系(HT22)评价其对抗压力因子损伤的作用。结果麋鹿角提取物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,以麋鹿角水提物的效用最强,该提取物能通过Erk信号通路,显著上调C6细胞中的NGF和BDNF的表达。此外,在皮质醇(Cortisol)损伤HT22的体外模型中,麋鹿角水提物具有显著的细胞保护作用,效果优于醇提物。结论麋鹿角对神经营养因子的调控和压力因子的调控是其抗抑郁的重要机制。Objective To investigate the mechanism of elk antler exerting anti-depression effect via regulation of neurotrophic factors and stress factors.Methods Elk antler extracts were prepared with water or ethanol.The antidepressive effects of elk antler extracts were evaluated on chronic unexpected mild stress(CUMS)induced depressionlike mice by sucrose preference test,tail suspension test and forced swimming test.The expressions of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)in hippocampus were determined by ELISA.The amounts of corticotrophin releasing hormone(CRF),adrenocorticotropic hormone(ACTH)and corticosterone(Cort)were also determined in serum by ELISA.Rat astroglioma cell lines(C6)were used to evaluate the effect of elk antler on regulating neurotrophic factor expressions.Mouse hippocampal immortalized cell lines(HT22)were established to evaluate the protective effect of the elk antler on stress neuronal damages.Results Elk antler extracts could significantly increase sucrose preference rate and decrease the immobile time of tail suspension and forced swimming on CUMS induced depression-like mice and the water extracts show the better effect.The water extract of elk antler could significantly increase the expressions of NGF and BDNF on C6 cells via Erk-dependent signaling pathway.In addition,the water extract of elk antler could protect HT22 neuronal cells from cortisol damages.The effect of water extracts was also superior to ethanol extracts.Conclusion Regulation of neurotrophic factors and stress factors might contribute to the antidepressive effect of elk antler.

关 键 词：麋鹿角 神经营养因子 压力因子 抑郁症 

分 类 号：R2-031[医药卫生—中西医结合]