大豆异黄酮调节HMGB1/RAGE信号通路对溃疡性结肠炎大鼠免疫功能的影响  

Effects of soybean isoflavones on immune function of rats with ulcerative colitis by regulating HMGB1/RAGE signal pathway

作　　者：邢启峰 周金芳 张士伟 XING Qifeng;ZHOU Jinfang;ZHANG Shiwei(Pharmacy Department of Tengzhou Central People's Hospital,Tengzhou 277599,China)

机构地区：[1]滕州市中心人民医院药学部,滕州277599

出　　处：《中国免疫学杂志》2025年第4期834-840,共7页Chinese Journal of Immunology

摘　　要：目的:探究大豆异黄酮(SIF)调节高迁移率族蛋白B1(HMGB1)/晚期糖基化终产物受体(RAGE)信号通路对溃疡性结肠炎(UC)大鼠免疫功能的作用。方法:将60只SD大鼠随机分为模型组(Model组),低、高剂量SIF组(SIF-L、H组,300、450 mg/kg SIF),高剂量SIF+HMGB1抑制剂甘草酸组(SIF-H+甘草酸组,450 mg/kg SIF+30 mg/kg甘草酸)和对照组(Control组),每组12只。采用TNBS/乙醇联合灌肠制备大鼠UC模型。测定各组大鼠体质量变化及疾病活动指数(DAI)。HE染色观察大鼠结肠组织病理学变化;比色法检测大鼠结肠组织超氧化物歧化酶(SOD)和丙二醛(MDA)水平;ELISA测定血清IL-1β、TNF-α、IL-4水平;流式细胞术测定外周血单个核细胞中CD3^(+)T、CD4^(+)T和CD8^(+)T淋巴细胞百分比;全自动特定蛋白分析仪测定血清IgA、IgG水平;Western blot、免疫组化法测定结肠组织HMGB1、RAGE蛋白表达。结果:相比Control组,Model组DAI、血清TNF-α、IL-1β水平、IgA、IgG水平、结肠组织MDA水平、结肠组织HMGB1、RAGE蛋白表达显著升高(P<0.05),SOD水平、IL-4、CD3^(+)T、CD4^(+)T和CD8^(+)T淋巴细胞百分比、CD4^(+)/CD8^(+)T显著降低(P<0.05),结肠组织黏膜出现破坏和损伤。与Model组相比,SIF-H组大鼠相关指标变化与上述相反(P<0.05),结肠组织损伤减轻。结论:SIF可能通过抑制HMGB1/RAGE信号通路,增强UC大鼠的免疫功能。Objective:To investigate the effects of soybean isoflavones(SIF)on immune function of rats with ulcerative colitis(UC)by regulating high-mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signal pathway.Methods:Sixty SD rats were randomly grouped into Model group,low dose SIF group(SIF-L group,300 mg/kg SIF),high dose SIF group(SIF-H group,450 mg/kg SIF),high dose SIF+HMGB1 inhibitor glycyrrhizic acid group(SIF-H+glycyrrhizic acid group,450 mg/kg SIF+30 mg/kg glycyrrhizic acid)and Control group,with 12 rats in each group.The UC rat model was established by TNBS/ethanol combined enema.Body weight changes of rats in each group were measured,and disease activity index(DAI)was determined in each group.Histopathological changes of colon were observed by HE staining;levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in colon tissue of rats were measured by colorimetry;serum levels of IL-1β,TNF-αand IL-4 were determined by ELISA;flow cytometry was used to determine the percentages of CD3^(+)T,CD4^(+)T and CD8^(+)T lymphocytes in peripheral blood mononuclear cells;levels of serum IgA and IgG were measured by automatic specific protein analyzer;expressions of HMGB1 and RAGE in colon tissues were determined by Western blot and immunohistochemistry.Results:Compared with Control group,levels of DAI,serum TNF-α,IL-1β,IgA,IgG,MDA in colon tissue,HMGB1 and RAGE protein expressions in colon tissue of Model group were obviously higher(P<0.05),while SOD level,IL-4,CD3^(+)T,CD4^(+)T and CD8^(+)T lymphocyte percentages,CD4^(+)/CD8^(+)T were obviously lower(P<0.05),the mucosa of colon tissue was damaged.Compared with Model group,changes of relevant indexes in SIF-H group were contrary to the above(P<0.05),and the damage of colon tissue was alleviated.Conclusion:SIF may enhance the immune function of UC rats by inhibiting HMGB1/RAGE signal pathway.

关 键 词：大豆异黄酮 高迁移率族蛋白B1/晚期糖基化终产物受体信号通路 溃疡性结肠炎 免疫功能 

分 类 号：R285[医药卫生—中药学]