柴胡黄芩药对通过PSD95及CDK5调节伏隔核区NR2B发挥抗抑郁作用的研究  

Chaihu-huangqin Herbal Pair Exhibits Antidepressant-like Effects and Regulates NR2B of Accumbens via PSD95 and CDK5 Related Mechanisms

作　　者：王上 明浩 王建婷 刘昊 陈新 岳滢滢 许乐思 周贤 刘松林 陈雨 WANG Shang;MING Hao;WANG Jian-ting;LIU Hao;CHEN Xin;YUE Ying-ying;XU Le-si;ZHOU Xian;LIU Song-lin;CHEN Yu(Clinical College of Chinese Medicine,Hubei University of Chinese Medicine,Wuhan,Hubei,430061,China;College of Pharmacy,Hubei University of Chinese Medicine,Wuhan,Hubei 430065,China;School of Medicine,Jianghan University,Wuhan,Hubei 430056,China)

机构地区：[1]湖北中医药大学中医临床学院,湖北武汉430061 [2]湖北中医药大学药学院,湖北武汉430065 [3]江汉大学医学院,湖北武汉430056

出　　处：《时珍国医国药》2020年第12期2828-2831,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81403127,81573960)。

摘　　要：目的评价柴胡黄芩药对的抗抑郁作用,探讨其对奖赏环路的作用,以揭示其治疗情志疾病的机制。方法制作CUMS大鼠模型,分别予1.05g/kg, 3.15g/kg, 9.45g/kg以柴胡黄芩药对及1.5 mg/kg予氟西汀进行治疗1周,然后分别检测旷场实验、糖水偏好实验和强迫游泳实验。Western检测NAc区的总NR2B,膜NR2B,PSD95和CDK5水平。结果各浓度的柴胡黄芩药对均能改善CUMS大鼠的抑郁样行为。总NR2B,膜NR2B,PSD95和CDK5的病程水平改变能够被柴胡黄芩药对逆转。结论奖赏环路的伏隔核区可能是柴胡黄芩药对的作用靶点,其机制可能与药对通过PSD95和CDK5调节膜NR2B实现。Objective The aim of this research was to evaluate the effect of CHHQ herbal pair on antidepressive behavior and accumbens, the core part of reward circuitry, to explore the underlying mechanisms of CHHQ herbal pair in mood disorder treatment. Methods A rat model of CUMS was established and treated with 1.05 g/kg, 3.15 g/kg, 9.45 g/kg CHHQ herbal pair and fluoxetine 1.5 mg/kg separately. The behavior assessment(open field test, sucrose preference test and forced swimming test) were used to evaluate the therapeutic effect on depressive disorder behavior. The expression of total and membrane NR2 B, PSD 95 and CDK5 were measured by Western blotting(WB). Results Administration of CHHQ herbal pair alleviates depressive-like behavior. The decreased level of total and membrane NR2 B was detected in the accumbens of chronic unpredictable mild stress(CUMS) rats. Those changes were restored via PSD 95 and/or CDK5 signaling pathway, which depend on the concentration of the herbal pair. Fluoxetine cannot decrease the elevation of CDK5 in NAc in CUMS.Conclusion The accumbens of reward circuitry may be the target of CHHQ herbal pair which regulates membrane NR2 B abnormality in clinical treatment on depressive disorder.

关 键 词：柴胡-黄芩药对 奖赏环路 伏隔核 突触可塑性 抑郁 

分 类 号：R285.5[医药卫生—中药学]