淫羊藿苷调节大鼠脑内N-甲基-D-天冬氨酸受体分子机制研究  

Molecular Mechanism of Icariin Regulating the NMDA Receptor in the Brain of Rats

作　　者：陈静 高瑜 夏海建 黄富宏[1] 王蓓蓓 CHEN Jing;GAO Yu;XIA Haijian;HUANG Fuhong;WANG Beibei(Department of Pharmacy,Affiliated Hospital of Yangzhou University,Yangzhou,Jiangsu,China 225001)

机构地区：[1]扬州大学附属医院药剂科,江苏扬州225001

出　　处：《中国药业》2020年第11期18-21,共4页China Pharmaceuticals

基　　金：江苏省扬州市科技计划项目[YZ2016131]。

摘　　要：目的探讨淫羊藿苷对大鼠海马体中脑源性神经营养因子(BDNF)/TrkB下游信号通路的调节作用,以及其调节N-甲基-D-天冬氨酸(NMDA)受体可能的分子机制。方法应用MK-801处理未成年大鼠,构建精神分裂症动物模型。大鼠口服淫羊藿苷2周,采用蛋白质印迹(WB)法检测淫羊藿苷对BDNF、TrkB及其下游PKC/Raf-1/ERK信号通路及NMDA受体蛋白表达的调节作用。结果MK-801可降低NMDA受体的表达水平,同时可抑制BDNF,TrkB,PKC,Raf-1,ERK1/2的表达水平;淫羊藿苷可逆转MK-801的作用,即上调上述蛋白的表达水平,其效果与现有抗精神病药利培酮相近。结论淫羊藿苷可能通过激活BDNF/TrkB介导PKC/Raf-1/ERK信号通路而增进NMDA受体的功能。Objective To investigate the regulatory effect of icariin on the downstream signal pathway of brain-derived neurotrophic factor(BDNF)/TrkB in rat hippocampus,and to explore the possible molecular mechanism of icariin regulating the N-methyl-D-aspartate(NMDA)receptor.Methods MK-801 and adolescent SD rats were used to establish the schizophrenia animal model.The rats were treated with icariin orally for two weeks.Western Blot(WB)was used to detect the regulatory effects of icariin on the expression of BDNF,TrkB and its downstream PKC/Raf-1/ERK signaling pathway,as well as NMDA receptors.Results MK-801 decreased NMDA receptor expression and inhibited the expression of BDNF,TrkB,PKC,Raf-1 and ERK1/2,respectively.Icariin could reverse the effects of MK-801,i.e.,up-regulate the expression of the aforementioned proteins,and its effects were similar to those of an existing antipsychotic drug-risperidone.Conclusion Icariin may enhance the function of the NMDA receptor by activating BDNF/TrkB-mediated PKC/Raf-1/ERK signaling pathway.

关 键 词：淫羊藿苷 脑源性神经营养因子 N-甲基-D-天冬氨酸受体 精神分裂症 大鼠 

分 类 号：R965[医药卫生—药理学] R971[医药卫生—药学]