The Modulatory Effect of Yulian Pills on Memory Follicular Helper T Cells in Mice with Dextran Sulfate Sodium-Induced Ulcerative Colitis / 中药新药与临床药理

ABSTRACT

Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P＜0.01),a significant shortening of colon length(P＜0.01),significant increase in colon mass(P＜0.05)and colon mass index(P＜0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P＜0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P＜0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P＜0.05),a significant extension of colon length(P＜0.01),a significant reduction in colon mass(P＜0.05),a significant decrease in the colon mass index(P＜0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P＜0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P＜0.05,P＜0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.