柴芍开郁汤通过补体C3/C3aR通路改善抑郁模型大鼠海马神经炎症的研究  

Mechanism of Chaishao Kaiyu Decoction in ameliorating hippocampal neuroinflammation in depressed rats based on complement component C3/C3aR pathway

作　　者：唐璎娟 郭海鹏 邹蔓姝 韩远山[2,3] 刘峻呈 王宇红 TANG Ying-juan;GUO Hai-peng;ZOU Man-shu;HAN Yuan-shan;LIU Jun-cheng;WANG Yu-hong(Technology Innovation Center,Hunan University of Chinese Medicine,Changsha 410208,China;the First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hunan Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Depressive Diseases,Changsha 410208,China;Pengzhou Hospital of Traditional Chinese Medicine,Chengdu 611930,China)

机构地区：[1]湖南中医药大学科技创新中心,湖南长沙410208 [2]湖南中医药大学第一附属医院,湖南长沙410007 [3]抑郁类疾病中医药防治湖南省重点实验室,湖南长沙410208 [4]彭州市中医医院,四川成都611930

出　　处：《中国中药杂志》2025年第1期1-9,共9页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82174357,82104846);湖南省中医药管理局科研项目(B2023141);湖南省科药联合基金项目(2023JJ60476);湖南省教育厅优秀青年基金项目(23B0360);学科建设“揭榜挂帅”项目(22JBZ06);湖南省卫健委一般项目(W20243097)。

摘　　要：基于补体C3(C3)/补体成分C3受体(C3aR),探讨柴芍开郁汤改善抑郁模型大鼠海马神经炎症的作用机制。SD大鼠60只,随机分为空白组,模型组,柴芍开郁汤高、中、低剂量组,阳性药组,每组10只,除空白组外,其余各组采用慢性不可预知应激(CUMS)法构建抑郁模型。以蔗糖偏嗜度、旷场实验、强迫游泳实验、水迷宫实验检测各组大鼠抑郁样行为变化。以酶联免疫吸附测定法(ELISA)检测大鼠血清炎症因子水平;苏木素-伊红(HE)染色和Nissl染色观察海马神经元病理损伤;高尔基染色观察海马神经元树突棘损伤情况;免疫荧光、Western blot检测小胶质细胞标记物离子钙结合衔接分子1(Iba-1)及大鼠海马中C3/C3aR蛋白的表达情况。行为学结果显示,与模型组比较,柴芍开郁汤能显著提高抑郁大鼠糖水偏嗜度,增加自主活动距离和活动次数,缩短强迫游泳的不动时间和定位航行的成功潜伏期,延长空间探索在目标象限停留的时间;ELISA结果显示,抑郁模型大鼠海马中炎症因子含量明显高于空白组,经柴芍开郁汤干预后,炎症因子含量明显降低;此外,柴芍开郁汤还能缓解海马组织胞体肿胀、排列松散等病理损伤;在Western blot实验中,模型组的C3、C3aR蛋白表达水平相较于空白组有所升高,而柴芍开郁汤能下调C3、C3aR的表达;免疫荧光结果显示,与模型组比较,经柴芍开郁汤和阳性药干预后小胶质细胞标记物Iba-1的荧光强度明显降低。柴芍开郁汤的抗抑郁作用可能与其下调C3/C3aR信号通路相关蛋白,进而缓解海马炎症反应有关。This study investigated the mechanism of Chaishao Kaiyu Decoction in improving hippocampal neuroinflammation in depressed rats based on complement component 3(C3)/C3 receptor(C3aR).A total of 60 SD rats were randomly divided into a blank group,a model group,high,medium,and low dose groups of Chaishao Kaiyu Decoction,and a positive drug group,with 10 rats in each group.Except for the blank group,chronic unpredictable mild stress(CUMS)was used to construct depression models in other groups.Sucrose preference,open-field experiment,forced swimming,and water maze were used to detect the changes in depression-like behavior in each group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum inflammatory factor level in rats,and hematoxylin-eosin(HE)staining and Nissl staining were employed to observe the pathological damage of hippocampal neurons.Golgi-Cox staining was used to observe the dendritic spine damage of hippocampal neurons,and immunofluorescence and Western blot were utilized to detect the expression of microglial marker Iba-1 and C3/C3aR protein in the hippocampus of rats.The behavioral results showed that compared with the model group,Chaishao Kaiyu Decoction could significantly strengthen the sugar water preference,increase the distance and number of voluntary activities,shorten the immobility time in forced swimming and the successful incubation period of positioning navigation,and prolong the stay time of space exploration in the target quadrant.ELISA results showed that the content of inflammatory factors in the hippocampus of depressed rats was significantly higher than that of the blank group,and the content of inflammatory factors decreased significantly after the intervention of Chaishao Kaiyu Decoction.In addition,Chaishao Kaiyu Decoction could relieve pathological damage such as cell swelling and loose arrangement of hippocampus tissue.In the Western blot experiment,the expression levels of C3 and C3aR proteins in the model group were higher than those in the blank group,while the e

关 键 词：抑郁症 海马 神经炎性损伤 C3/C3aR 柴芍开郁汤 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]