Therapeutic effect of Xianglian Zhixie tablet on oxazolone-induced ulcerative colitis in mice
Objective To investigate the therapeutic effect of Xianglian Zhixie tablet on oxazolone-induced ulcerative colitis(UC)in mice,and to explore its mechanism of action based on the Th1/Th2 immune axis.Methods Forty-eight male BALB/c mice were selected and were randomly divided into the blank control group,model group,mesalazine group,low-dose Xianglian Zhixie tablet group,medium-dose Xianglian Zhixie tablet group,and high-dose Xianglian Zhixie tablet group,with eight mice in each group.The mice in the model group,mesalazine group,low-dose,medium-dose,and high-dose Xianglian Zhixie tablet groups were treated with oxazolone to induce UC.The mice in the blank control group were not treated.From the first day of the establishment of UC model,the mice were given intragastric administration once a day for seven days.Mice in the mesalazine group were given mesalazine at the dosage of 0.31 g/kg;mice in the low-dose Xianglian Zhixie tablet group,medium-dose Xianglian Zhixie tablet group,and high-dose Xianglian Zhixie tablet group were given Xianglian Zhixie tablets at the dosage of 0.68,1.36,and 2.72 g/kg,respectively;mice in the blank control group and the model group were given an equal amount of purified water.During the administration,the disease activity index(DAI)scores were performed daily.At the end of last administration,the body mass was weighted.After anesthesia,the mouse's abdominal cavity was opened,the spleen was separated and weighed,and the spleen index was calculated.The colon was separated,and the length of the entire colon segment was measured.The part of colon tissues was taken and stained by peri-odic acid-schiff.The pathological changes of the colon were observed,and the number of goblet cells of the colonic mucosa were counted by periodic acid-schiff(PAS)staining.The levels of interleukin(IL)-1β and tumor necrosis factor-α(TNF-α)in colon were detected by ELISA.The protein expression levels of interferon(IFN)-γ and IL-4 in colon were detected by Western blotting.The proportions of Th1 and Th2 cells in the plasma was detected by flow cytometry,and Th1/Th2 was cal-culated.Results Compared with the blank control group,DAI score,spleen index,the levels of IL-1β and TNF-α,the protein expression level of IFN-γ,whole blood Th1 cell ratio,and Th1/Th2 significantly increased,the number of goblet cells of the colonic mucosa decreased,the arrangement was irregular,the glycogen content,colon length,protein expres-sion level of IL-4,and whole blood Th2 cell ratio significantly decreased in the model group(all P<0.05).Compared with the model group,DAI score,spleen index,the levels of IL-1β and TNF-α,the proportion of whole blood Th1 cells,and Th1/Th2 significantly decreased,the number of goblet cells of the colonic mucosa significantly increased,the morphology was intact,and the glycogen content tended to be normal,the shortening of colon length was significantly inhibited,and the protein expression level of IL-4 was significantly up-regulated in the Xianglian Zhixie tablet groups and mesalazine group(all P<0.05).Conclusions Different dosages of Xianglian Zhixie tablet have a certain therapeutic effect on oxazolone-induced UC in mice,and the effect of high dose(twice the clinical equivalent dose)of Xianglian Zhixie tablet group is bet-ter.Regulating the Th1/Th2 immune axis,thereby reducing intestinal inflammation,may be one of the mechanisms of action of Xianglian Zhixie tablets.