Study on the Dynamic Changes of Inflammatory Factors in Chronic Stress Mice and the Effect of Xiaoyao San

XUE Qianyin; WU Shuya; ZHANG Yi; XU Jingyu; LI Guohui; WANG Xinrong; ZHANG Mingjia; AO Haiqing

Abstract：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)-β were 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-β levels 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-β and 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-β level 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.