基于BDNF/HPA调节机制探究逍遥丸对CUMS模型大鼠的抗抑郁作用  

Study on the anti-depressant effects of Xiaoyao pill in a rate model of CUMS based on BDNF/HPA mechanism

作　　者：谢红潇 秦甜甜 姜燕宁 曾南[1] 刘蓉[1] XIE Hongxiao;QIN Tiantian;JIANG Yanning;ZENG Nan;LIU Rong(State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Sichuan Chengdu 611137,China)

机构地区：[1]西南特色中药资源国家重点实验室,成都中医药大学药学院,四川成都611137

出　　处：《中药与临床》2025年第1期36-45,共10页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(82074094);四川省科技厅应用基础研究项目(2020YJ0388)。

摘　　要：目的:探究逍遥丸对CUMS大鼠模型的抗抑郁作用及机制。方法:将雄性Wistar大鼠随机分为空白组、模型组、逍遥丸组及阿米替林组,采用慢性温和不可预知应激4周建立CUMS模型,造模成功后,各给药组连续灌胃4周。以糖水偏好实验、旷场实验、强迫游泳及Morris水迷宫实验观察逍遥丸对CUMS大鼠行为学的影响;酶联免疫吸附测定法测定HPA轴相关激素和BDNF、TrkB、CREB的水平;RT-PCR和Western-Blot法测定皮层、海马BDNF、TrkB、CREB、GR的mRNA和蛋白表达。结果:与模型组比较,逍遥丸组大鼠糖水偏好率和旷场中的运动时间、距离和站立次数显著升高;强迫游泳不动时间和水迷宫实验中的空间搜索潜伏期显著缩短,在原平台所在象限的游泳时间和距离显著增加。此外,逍遥丸可显著上调CUMS大鼠的BDNF、TrkB和CREB水平,促进CREB磷酸化;降低CUMS大鼠肾上腺指数、Cort、CRH和ACTH水平以及GR表达水平。结论:逍遥丸能改善CUMS大鼠的抑郁样行为,该作用可能与其抑制HPA轴功能亢进、上调BDNF功能有关,为临床应用提供药理学依据。Objective:To investigate the antidepressant effect and mechanism of Xiaoyao pill on CUMS rat model.Methods:Male Wistar rats were randomly divided into control group,model group,amnripoyline group,Xiaoyao pill group,and the CUMS model was established by using chronic mild and unpredictable stress for 4 weeks.The successfully modeled mice in the medication groups were intragastrically administered with the corresponding drugs.The effect of Xiaoyao pill on behavior in CUMS rats were observed by experiments of sucrose preference test(SPT),open field test(OFT),forced swim test(FST)and morris water maze test.The levels of HPA hormones and BDNF,TrkB and CREB were measured by ELISA.The mRNA and protein expressions of cortex and hippocampal BDNF,TrkB,CREB,and GR were determined by RT-PCR and Western-Blot methods.Results:Compared with the model group,the sugar-water preference rate,and the exercise time,distance and number of standing in the OFT were significantly higher in Xiaoyao pill group.The immobility time and the escape latency in morris water maze were significantly decreased.The swimming time and distance in the quadrant where the original platform was located were significantly increased.In addition,Xiaoyao pill significantly up-regulated the levels of BDNF,TrkB,and CREB and promoted CREB phosphorylation.It also decreased the levels of adrenal index,Cort,CRH,and ACTH,as well as decreased the level of GR expression in CUMS rats.Conclusion:Xiaoyao pill can improve depressive behavior in CUMS-induced rats,which may be related to the inhibition of HPA axis hyperfunction and the upregulation of BDNF function.The study provides pharmacological basis for clinical application.

关 键 词：逍遥丸 慢性不可预测轻度应激 脑源性神经营养因子 下丘脑-垂体-肾上腺轴 抑郁 机制 

分 类 号：R285.5[医药卫生—中药学]