百合地黄汤激活AMPA受体改善慢性不可预见性应激小鼠焦虑和抑郁样行为的机制  

Mechanism of Baihe Dihuang Decoction activating AMPA receptor to improve anxiety and depression-like behavior in chronic unpredictability stress mice

作　　者：赵洪庆[1] 唐林[2] 刘洋[1] 姜嘉琪 吕蕤丹 刘检[2] 龙红萍[2] 王宇红[1] ZHAO Hong-qing;TANG Lin;LIU Yang;JIANG Jia-qi;LYU Rui-dan;LIU Jian;LONG Hong-ping;WANG Yu-hong(Hunan University of Chinese Medicine,Changsha 410208,China;The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,China)

机构地区：[1]湖南中医药大学,长沙410208 [2]湖南中医药大学第一附属医院,长沙410007

出　　处：《中华中医药杂志》2023年第5期1955-1960,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82174357,No.82104836,No.82104793);中医学一流学科开放基金项目(No.2022ZYX18);中药粉体与创新药物国家重点实验室培育基地开放基金项目(No.21PTKF1017)。

摘　　要：目的:探明百合地黄汤通过激活AMPA受体发挥抗焦虑抑郁药效的机制。方法:采用慢性不可预见性应激诱导小鼠的焦虑和抑郁样行为,施加高、中、低剂量(16、8、4 g/kg)的百合地黄汤干预。采用高架十字迷宫评价小鼠焦虑样行为,糖水偏好实验和强迫游泳实验评价抑郁样行为,高尔基染色观察突触形态,免疫组化和Western Blot法检测海马AMPA受体亚基GluA1、GluA2及其下游信号的表达。并采用AMPA受体阻断剂NBQX评估AMPA受体在百合地黄汤药效中的作用。结果:与正常组比较,模型组小鼠进入开放臂次数比(OE%)及停留时间比(OE%)均显著下降(P<0.01),糖水偏好度降低(P<0.01),强迫游泳不动时间显著增加(P<0.01),表现出明显的焦虑和抑郁样行为,海马GluA1、GluA2及其下游p-CREB、BDNF表达均显著降低(P<0.01),突触结构受损;百合地黄汤高剂量干预后,海马GluA1、GluA2及p-CREB、BDNF表达均显著增加(P<0.01,P<0.05),突触复杂性得以恢复。模型小鼠的焦虑抑郁样行为显著改善,但该作用可被NBQX阻断。结论:百合地黄汤通过激活海马AMPA受体表达,改善突触可塑性损伤,发挥抗焦虑抑郁作用。Objective:To investigate the mechanism of Baihe Dihuang Decoction exerts its anti-anxiety and anti-depression effect by activating AMPA receptor.Methods:Anxiety and depression-like behavior were induced by chronic unpredictability stress in mice,and high,medium and low doses(16,8,4 g/kg)of Baihe Dihuang Decoction were administered.The anxiety-like behavior of mice was evaluated by the elevated cross maze,the depression-like behavior of mice was evaluated by the sugar water preference test and the forced swimming test,the synaptic morphology was observed by Golgi staining,and the expressions of GluA1,GluA2 and their downstream signals of the hippohippoal AMPA receptor subunits were detected by immunohistochemistry and Western Blot.The role of AMPA receptor in Baihe Dihuang Decoction was evaluated by using the AMPA receptor blocker NBQX.Results:Compared with the normal group,the ratio of times of entering the open arm(OE%)and retention time(OE%)in model group were significantly decreased(P<0.01),the sugar water preference was decreased(P<0.01),the immobile time of forced swimming was significantly increased(P<0.01),and the mice showed obvious anxiety and depressionlike behavior.The expressions of GluA1,GluA2 and their downstream p-CREB and BDNF in hippocampus were significantly decreased(P<0.01),and synaptic structure was damaged.After the intervention of high dose Baihe Dihuang Decoction,the expressions of GluA1,GluA2,p-CREB and BDNF in hippocampus were significantly increased(P<0.01,P<0.05),the synaptic complexity was restored.The anxietic-depression-like behavior of model mice was significantly improved,but the above effects could be blocked by NBQX.Conclusion:Baihe Dihuang Decoction can improve synaptic plasticity by activating hippocampal AMPA receptor expression and play an anti-anxiety and depression role.

关 键 词：百合地黄汤 焦虑 抑郁 AMPA受体 突触 

分 类 号：R285.5[医药卫生—中药学]