基础医学与临床2025，Vol.45Issue(8)：1022-1027,6.DOI:10.16352/j.issn.1001-6325.2025.08.1022
高脂饮食加重小鼠肠易激综合征肠屏障损伤
High fat diet aggravates intestinal barrier damage in mice with irritable bowel syndrome
摘要
Abstract
Objective To explore the effects and underlying molecular mechanisms of high fat diet(HFD)on in-testinal barrier damage and inflammatory reaction in mice with irritable bowel syndrome(IBS)induced by sodium dextran sulfate(DSS).Methods C57BL/6 mice were randomly divided into four groups(n=6):Normal group,DSS group(1.5％DSS solution for one week),HFD+DSS group,and HFD+DSS+WY14643 group(intraperitone-ally injected daily with PPARα agonist WY14643 6 mg/kg).The body weight and liver weight of mice were measured.Colon pathology was observed by HE staining.The protein expression of zonula occludens-1(ZO-1)and occludin was detected by immunohistochemistry.The mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-β(IL-1β),and interleukin-17(IL-17)were determined by qRT-PCR.PPARα protein expression was determined by Western blot.Results The body weight and liver weight of mice in the HFD+DSS group were significantly higher than those in the DSS group(P＜0.001).HE staining showed normal colonic tissue structure in Normal group,while other three groups exhibited varying degrees of mucosal damage with a small amount of in-flammatory cell infiltration and epithelial cell shedding.Among these,the HFD+DSS group displayed the most se-vere intestinal mucosal damage and inflammatory infiltration.Compared with the DSS group,the HFD+DSS group showed decreased ZO-1 and Occludin protein expression(P＜0.001),elevated TNF-α,IL-1 β,and IL-17 mRNA levels(all P＜0.001),and downregulated PPARα protein expression(P＜0.01).Compared with the HFD+DSS group,mice in HFD+DSS+WY14643 group showed improvement in intestinal mucosal damage and reduced infiltration of inflammatory cells.The protein expression of ZO-1 and occludin in colon of mice in the HFD+DSS+WY14643 was increased(all P＜0.05),while the expression of TNF-α,IL-1 β,and IL-17 mRNA was downregulated(P＜0.01 or P＜0.05),and the protein expression of PPAR α was upregulated(P＜0.05).Conclusions HFD-induced obesity aggravates intestinal mucosal damage,intestinal barrier destruction and in-flammatory response in IBS mice,and its molecular mechanism is potentially related to downregulation of PPARαexpression in intestinal tissues.关键词
肠易激综合征/肥胖/过氧化物酶体增殖物激活受体α/肠屏障损伤/炎性因子Key words
irritable bowel syndrome/obesity/peroxisome proliferator-activated receptor-α/intestinal barrier damage/inflammatory factors分类
医药卫生引用本文复制引用
赵翠娟,敖民,武文博,李妍华..高脂饮食加重小鼠肠易激综合征肠屏障损伤[J].基础医学与临床,2025,45(8):1022-1027,6.基金项目
内蒙古自治区科技计划项目(2022YFSH0042) （2022YFSH0042）
航天医疗健康科技集团有限公司科研项目(2023YK22) （2023YK22）
内蒙古医学科学院公立医院科研联合基金科技项目(2023GLLH0242) （2023GLLH0242）
