基于IL33/ST2信号通路探究芍药汤对溃疡性结肠炎大鼠的干预效果

Investigation of the intervention effect of Shaoyao Decoction on rats with ulcerative colitis based on IL-33/ST2 signaling pathway

目的分析基于白介素-33(IL-33)ST2信号通路探究芍药汤对溃疡性结肠炎大鼠的干预效果。方法选购50只SPF级SD大鼠,随机分为正常组(A组)、溃疡性胃炎模型组(B组)、低剂量芍药汤组(C组)、中剂量芍药汤组(D组)、高剂量芍药汤组(E组)。造模成功后对C、D、E组灌胃,确定芍药汤低、中、高剂量。A组与B组均予等量0.9%氯化钠溶液灌胃。各组连续干预7 d。收集大鼠血清及结肠组织切片,测定结肠组织免疫球蛋白A(SIgA)、CD4^(+)T淋巴细胞、亚型前列腺素过氧化物合成酶(COX-2)表达,检测血清内皮素(ET)、白介素-4(IL-4)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β_(1)(TGF-β_(1))、细胞间黏附分子(iICAM-1)表达及IL-33、ST2蛋白表达。结果与A组相比,B组SIgA、CD4^(+)、TGF-β_(1)水平降低,COX-2、ET、IL-4、TNF-α、ICAM-1、IL-33、ST2水平升高;与B组相比,C、D、E组SIgA、CD4^(+)、TGF-β_(1)水平升高,COX-2、ET、IL-4、TNF-α、ICAM-1、IL-33、ST2水平降低;E组SIgA、CD4^(+)、TGF-β_(1)水平升高,COX-2、ET、IL-4、TNF-α、ICAM-1、IL-33、ST2水平降低,优于C、D组(P<0.05)。结论芍药汤能下调IL33/ST2表达,抑制IL-33/ST2介导炎症反应,改善免疫反应,减少肠黏膜病理损伤,发挥黏膜保护机制,治疗效果显著。

Objective To analyze the intervention effect of Shaoyao Decoction on rats with ulcerative colitis based on the interleukin-33(IL-33)/ST2 signaling pathway.Methods A total of fifty SPF SD rats were selected and randomly divided into a normal group(group A),an ulcerative gastritis model group(group B),a low-dose Shaoyao Decoction group(group C),a middle-dose Shaoyao Decoction group(group D),and a high-dose Shaoyao Decoction group(group E).After successful modeling,groups C,D,and E were given the corresponding low,medium and high doses of Shaoyao Decoction by gavage,while groups A and B were given the same amount of 0.9%sodium chloride solution by gavage.Each group was continuously intervened for 7 days.The rats serum and colon tissue sections were collected to determine the expressions of colon tissue immunoglobulin A(SIgA),CD4^(+)T lymphocytes,subtype prostaglandin peroxidase synthase(COX-2),and the expressions of serum endothelin(ET),interleukin-4(IL-4),tumor necrosis factor-α(TNF-α),transforming growth factor-β_(1)(TGF-β_(1)),intercellular adhesion molecule(iICAM-1),and the protein expressions of IL-33 and ST2 were detected.Results Compared with group A,the levels of SIgA,CD4^(+)and TGF-β_(1)in group B were decreased,while the levels of COX-2,ET,IL-4,TNF-α,ICAM-1,IL-33 and ST2 were increased.Compared with group B,the levels of SIgA,CD4^(+)and TGF-β_(1)were increased in groups C,D and E,while the levels of COX-2,ET,IL-4,TNF-α,ICAM-1,IL-33 and ST2 were decreased,and the levels of SIgA,CD4^(+),TGF-β_(1)in group E were increased,while the levels of COX-2,ET,IL-4,TNF-α,ICAM-1,IL-33,and ST2 were decreased,which were better than those in groups of C and D(P<0.05).Conclusion Shaoyao Decoction can down-regulate the expression of IL33/ST2,inhibit the inflammatory response mediated by the IL-33/ST2 signaling pathway,improve the immune response,reduce the pathological damages of intestinal mucosa,give play to the mucosal protective mechanism,having a significant therapeutic effect.