广西医科大学学报2024,Vol.41Issue(3):373-379,7.DOI:10.16190/j.cnki.45-1211/r.2024.03.008
三丁酸甘油酯通过抑制铁死亡缓解2,4,6-三硝基苯磺酸诱导的大鼠肠道炎症
Tributyrin alleviating 2,4,6-trinitrobenzene sulfonic acid-induced intestinal inflammation in rats by inhibiting ferroptosis
摘要
Abstract
Objective:To investigate the mechanism of tributyrin(TB)in alleviating 2,4,6-trinitrobenzene sulfon-ic acid(TNBS)-induced intestinal inflammation in rats with experimental colitis.Methods:A total of 24 male Sprague Dawley rats were randomly divided into four groups(6 rats in each group):control group,model group(TNBS group),low-dose TB group(TNBS+TB 600 mg/kg)and high-dose TB group(TNBS+TB 1,000 mg/kg),and the low-dose and high-dose TB groups were gavaged with the corresponding dose of TB for one week before and after modeling.After modeling,the rats were observed for activity and fecal characteristics,the rats were as-sessed for the disease activity index(DAI),and the colonic tissues were observed and stained with hematoxylin-eosin and scored for histological damage after the rats were put to death.Enzyme-linked immunosorbent assay(ELISA),western blotting,immunohistochemistry,and biochemical assays were used to assess the inflammation and the results of signaling pathways associated with ferroptosis.Results:Compared with the control group,the TNBS group had significantly higher DAI scores,histological damage scores,significantly lower protein expres-sion levels of GPX4 and SLC7A11,and higher expression levels of ACSL4 and FTH1.Low-and high-dose TB treatment significantly reduced DAI scores and histological damage scores compared with the TNBS group,with the best treatment effect in the high-dose TB group(all P<0.05).TB reversed the expression of glutathione and malondialdehyde in intestinal epithelial cells from the TNBS group and up-regulated the GPX4 and SLC7A11 protein expression levels while down-regulating the ACSL4 and FTH1 expression levels(all P<0.05).Conclu-sion:TB ameliorates oxidative stress and intestinal inflammatory damage in TNBS-induced Crohn's disease rats.Its mechanism may be related to the inhibition of the ferroptosis pathway.关键词
三丁酸甘油酯/克罗恩病/铁死亡/肠上皮细胞Key words
tributyrin/crohn's disease/ferroptosis/intestinal epithelial cells分类
医药卫生引用本文复制引用
黄子倩,吕晓丹,徐小芳,韩冰,詹灵凌,吕小平..三丁酸甘油酯通过抑制铁死亡缓解2,4,6-三硝基苯磺酸诱导的大鼠肠道炎症[J].广西医科大学学报,2024,41(3):373-379,7.基金项目
国家自然科学基金资助项目(No.81860104) (No.81860104)
广西自然科学基金资助项目(2023GXNSFDA026024) (2023GXNSFDA026024)