Shionone improves TNBS-induced Crohn's disease like colitis by inhibiting apoptosis of intestinal epithelial cells
Objective To investigate the effect and its possible mechanism of shionone(SHI)on Crohn's disease(CD)-like colitis induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS)in mice.Methods Eighteen wild-type mice were randomly divided into three groups:control group(WT group),model group(TNBS group),and SHI intervention group(SHI group),with 6 mice in each group.Mice in TNBS group were given 5％TNBS by anal injection to induce CD-like colitis,while mice in SHI group were given SHI[40 mg/(kg·d)]by gavage at the same time of TNBS modeling,and mice in WT group and TNBS group were given equal volume of normal saline by gavage daily.One week later,the mice were euthanized and the severity of colitis was evaluated by disease activity(DAI)score,body mass change,colon length,histological inflammation score,and the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1 β(IL-1 β)in mouse colon mucosa.Intestinal barrier function was evaluated by fluorescein isothiocyanate-dextran(FITC)permeability,intestinal fatty acid-binding protein(Ⅰ-FABP)and bacterial displacement rate.The apoptosis of intestinal epithelial cells in each group was detected by TUNEL staining.The expressions of apoptosis-related proteins(Bcl-2 and Bax)in each group were detected by Western blot.The protective effect of SHI intervention against CD-like colitis in mice was predicted by network pharmacology and biogenic enrichment analysis.Results Compared with WT group,DAI score,body mass reduction,histological inflammation score and the levels of TNF-α,IL-6 and IL-1 β in colon mucosa were significantly increased in TNBS group(P＜0.05).Compared with TNBS group,DAI score,body mass reduction,histological inflammation score and the levels of TNF-α,IL-6 and IL-1 βin colon mucosa were significantly decreased in SHI group(P＜0.05).Compared with WT group,the colonic length was shortened in TNBS group(P＜0.05).Compared with TNBS group,the colonic length was increased in SHI group(P＜0.05).Network pharmacology and biogenic enrichment analysis showed that SHI may treat CD by antagonizing intestinal epithelial cell apoptosis.Compared with TNBS group,the levels of FITC-dextran and I-FABP in peripheral blood and the bacterial translocations in liver and mesenteric lymph nodes were decreased in SHI group(P＜0.05).TUNEL staining showed that compared with TNBS group,the number of apoptosis of midgut epithelial cells was significantly decreased in SHI group(P＜0.05),the expression of Bax was downregulated(P＜0.05),and the expression of Bcl-2 was upregulated(P＜0.05).Conclusion SHI may alleviate TNBS-induced CD-like colitis in mice by inhibiting the apoptosis of intestinal epithelial cells.
万方数据
维普
