基于NLRP1炎症小体探讨百合知母汤抗抑郁的作用机制  

Exploration of the antidepressant mechanism of Baihe Zhimu decoction based on NLRP1 inflammasome

作　　者：岳春华 贲永光 王海桥[2] YUE Chunhua;BEN Yongguang;WANG Haiqiao(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China;Department of Traditional Chinese Medicine,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 201112,China)

机构地区：[1]广东药科大学药学院,广东广州510006 [2]上海交通大学医学院附属仁济医院中医科,上海201112

出　　处：《药学实践与服务》2024年第8期325-333,共9页Journal of Pharmaceutical Practice and Service

基　　金：国家自然科学基金(82274254);广东省中医药局科研项目(20221220)。

摘　　要：目的基于NLRP1炎症小体研究百合知母汤抗抑郁的作用机制。方法构建慢性不可预测轻度应激(CUMS)诱导的抑郁症小鼠模型,将C57BL/6J小鼠随机分为对照组、模型组、百合知母汤低剂量组、百合知母汤高剂量组以及MDP组(NLRP1激活剂)。连续给药4周,考察小鼠行为学特征。ELISA检测小鼠海马炎症因子IL-1β、IL-6、TNF-α和神经递质5-HT、NE、DA的水平。Western blot检测炎症小体相关蛋白NLRP1、ASC和caspase-1的表达,以及BDNF/TrkB和ERK/AKT/mTOR信号通路相关蛋白的变化,免疫荧光检测小鼠海马BDNF表达的变化。结果百合知母汤能抑制CUMS小鼠海马NLRP1炎症小体的活化,改善小鼠行为特征,提高小鼠海马神经递质水平,降低炎症反应。NLRP1激活剂MDP能逆转百合知母汤的上述作用。百合知母汤能上调下游分子BDNF、TrkB的表达水平,提高ERK、AKT和mTOR蛋白磷酸化水平,而MDP能逆转上述作用。结论百合知母汤通过抑制NLRP1炎症小体活化,抑制CUMS抑郁症小鼠海马神经炎症反应,进而激活BDNF/TrkB信号通路和ERK/AKT/mTOR信号通路来改善CUMS小鼠的抑郁样行为。Objective To study the mechanism of antidepressant effect of Baihe Zhimu decoction based on NLRP1 inflammasome.Methods A chronic unpredictable mild stress(CUMS)induced depression mouse model was constructed.C57BL/6J mice were randomly divided into a control group,CUMS group,low-dose Baihe Zhimu decoction group,high-dose Baihe Zhimu decoction group,and MDP group(NLRP1 activator).After continuous administration for 4 weeks,the behavioral characteristic of mice was investigated.The levels of mice hippocampal inflammatory factors IL-1β、IL-6,TNF-α,and neurotransmitters 5-HT,NE,and DA were detected by ELISA.The expression of inflammasome related proteins NLRP1,ASC,and caspase-1,as well as related proteins in BDNF/TrkB and ERK/AKT/mTOR signaling pathway were detected by Western blot.Immunofluorescence was used to detect changes in BDNF expression in the hippocampus of mice.Results Baihe Zhimu decoction inhibited the activation of NLRP1 inflammasomes in the hippocampus of CUMS mice,improved their behavioral characteristics,increased the level of neurotransmitters in the hippocampus,and reduced the inflammatory response.The NLRP1 activator MDP reversed the above effects of Baihe Zhimu decoction.Baihe Zhimu decoction increased BDNF,TrkB expression,and phosphorylation levels of ERK,AKT,and mTOR proteins,which could be reversed by MDP.Conclusion Baihe Zhimu decoction improved depression like behavior in CUMS mice by inhibiting NLRP1 inflammasome activation and hippocampal neuroinflammatory response,and thereby activating BDNF/TrkB and ERK/AKT/mTOR signaling pathway.

关 键 词：百合知母汤 抑郁症 炎症反应 NLRP1炎症小体 BDNF/TrkB信号通路 

分 类 号：R285.5[医药卫生—中药学]