摘要
目的 探讨慢性应激小鼠炎症因子水平的动态变化及逍遥散的免疫调节机制。方法 采用慢性温和不可预知刺激(CUMS)建立应激小鼠模型,观察应激造模第1~5周及逍遥散干预后小鼠体质量和脾脏指数变化;通过糖水偏好实验和旷场实验评价小鼠行为学改变;ELISA法检测血清皮质酮(CORT)、白细胞介素(IL)-6、IL-10、IL-17A和转化生长因子(TGF)-β水平。结果 与对照组比较,应激后模型小鼠体质量(P<0.05)、旷场实验中央路程(P<0.05)、糖水偏爱率(P<0.05)均在第3、4、5周显著降低;脾脏指数(P<0.01)和旷场实验总路程(P<0.01)均在第4、5周降低;血清CORT水平在第1、2、4、5周升高(P<0.01);IL-6水平在第2、3、4、5周升高(P<0.05);IL-17A水平在各时间点均升高(P<0.05);TGF-β水平在第1、4、5周升高(P<0.05);IL-10水平在第4、5周升高(P<0.01);IL-17A/IL-10比值在第2、3、4、5周升高(P<0.05)。应激后第2周是免疫激活相关细胞因子峰值期,同时也是免疫抑制相关细胞因子谷值期。应激5周后,与实验组比较,逍遥散高剂量组体质量、旷场实验总路程、中央路程和糖水偏爱率均升高(P<0.01),脾脏指数与血清CORT、IL-6、IL-17A、TGF-β、IL-10水平均降低(P<0.05);逍遥散低剂量组旷场实验中央路程和糖水偏爱率均升高(P<0.05),血清IL-10水平降低(P<0.05)。应激后,小鼠旷场实验中央路程与TGF-β水平呈正相关,与L-17A/IL-10比值呈负相关。结论 慢性应激可诱导小鼠免疫激活状态,逍遥散可能通过抑制下丘脑-垂体-肾上腺(HPA)轴活性,降低CORT水平来缓解免疫激活,从而发挥抗应激损伤的作用。
Objective To investigate the dynamic changes of inflammatory factors in chronic stress mice and the immunoregulatory mechanism of Xiaoyao San.Methods The chronic unpredictable mild stress(CUMS)model was established.Body weight and spleen index were measured during weeks 1-5 of modeling and after Xiaoyao San intervention.Behavioral changes were evaluated by sucrose preference test and open field test.Serum levels of corticosterone(CORT),interleukin(IL)-6,IL-10,IL-17A and transforming growth factor(TGF)-βwere detected by ELISA.Results Compared with the control group,the model group showed significant decreases in body weight(P<0.05),central distance in open field test(P<0.05)and sucrose preference rate(P<0.05)during weeks 3-5;reduced spleen index(P<0.01)and total distance in open field test(P<0.01)during weeks 4-5;elevated serum CORT levels at weeks 1,2,4 and 5(P<0.01);increased IL-6 levels at weeks 2-5(P<0.05);elevated IL-17A levels at all time points(P<0.05);higher TGF-βlevels at weeks 1,4 and 5(P<0.05);increased IL-10 levels at weeks 4-5(P<0.01);and raised IL-17A/IL-10 ratio at weeks 2-5(P<0.05).Week 2 represented the peak period of pro-inflammatory cytokines and the trough period of anti-inflammatory cytokines.Compared with the model group,high-dose Xiaoyao San significantly improved body weight,total distance and central distance in open field test and sucrose preference(P<0.01),while decreasing spleen index and serum levels of CORT,IL-6,IL-17A,TGF-βand IL-10(P<0.05).Low-dose Xiaoyao San improved central distance and sucrose preference(P<0.05)while reducing IL-10 level(P<0.05).After stress,central distance in open field test positively correlated with TGF-βlevel but negatively correlated with IL-17A/IL-10 ratio.Conclusion Chronic stress induces immune activation in mice.Xiaoyao San may exert anti-stress effects by suppressing HPA axis activity and reducing CORT level,thereby alleviating immune activation.
作者
薛茜尹
吴淑雅
张怡
许婧余
李国辉
王欣荣
张铭珈
敖海清
XUE Qianyin;WU Shuya;ZHANG Yi;XU Jingyu;LI Guohui;WANG Xinrong;ZHANG Mingjia;AO Haiqing(School of Public Health and Management,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;School of Basic Medical Sciences,Zhejiang University of Chinese Medicine,Hangzhou 310053,China)
出处
《中国中医基础医学杂志》
2025年第7期1199-1203,共5页
JOURNAL OF BASIC CHINESE MEDICINE
基金
国家自然科学基金项目(81673838,82205229)
广东省区域联合基金-青年基金项目(2021A1515110798)
浙江中医药大学附属医院科研专项(402219A00205)
浙江中医药大学校级科研项目(711100E037)。
关键词
逍遥散
应激
慢性应激
免疫平衡
炎症因子
Xiaoyao San
Stress
Chronic stress
Immune balance
Inflammatory factors
