4-辛基衣康酸通过激活Nrf2减轻DSS诱导的溃疡性结肠炎

4-Octyl Itaconate Ameliorates Dextran Sodium Sulphate-Induced Ulcerative Colitis via Nrf2 Activation

该文主要研究4-辛基衣康酸对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的小鼠溃疡性结肠炎的保护效应。C57BL/6实验小鼠分为空白对照组、衣康酸药物对照组、DSS模型组和衣康酸+DSS干预组。每天观察小鼠体质量、便血情况、粪便性状。PAS染色和TUNEL染色观察小鼠肠黏液分泌和肠上皮细胞凋亡情况。Western blot检测核因子E2相关因子2(NF-E2-related factor 2,Nrf2)和醌氧化还原酶1(quinine oxidoreductase 1,NQO1)的表达。结果显示,与DSS模型组相比,衣康酸干预处理后,小鼠的体质量降低、便血、粪便黏稠和结肠缩短等病理损伤情况明显改善;肠黏膜分泌的黏液增多,肠上皮细胞凋亡数量减少;小鼠体内的抗氧化蛋白水平显著升高。从体质量下降、结肠缩短、疾病活动指数评分和肠黏膜损伤等方面进行评价,证实4-辛基衣康酸可在DSS诱导的结肠炎中发挥保护效应,其机制可能与Nrf2抗氧化通路的上调有关。

The aim of this study was to investigate the effect of 4-octyl itaconate on ulcerative colitis mice induced by DSS(dextran sulfate sodium).C57BL/6 mice were divided into control group,itaconate group,DSS-treated group and itaconate+DSS-treated group.Body mass,hematochezia,fecal characteristics of mice were daily observed.PAS and TUNEL staining were applied to detect the intestinal mucous secretion and cell apoptosis.The expression of Nrf2(NF-E2-related factor 2)and NQO1(quinine oxidoreductase 1)were analyzed by Western blot.Compared with DSS mice,the itaconate+DSS-treated group presented evident improvement on body mass loss,hematochezia,fecal characteristics,colon shortening and other pathological injuries;showing more mucus and decreased TUNEL positive cells;and the expression levels of antioxidant protein were significantly increased.The evaluation was based on body mass loss,colon shortening,DAI score and the intestinal mucosal injury.These results demonstrate that 4-octyl itaconate possess positive effect on DSS-induced ulcerative colitis,and the mechanism may be related to the up-regulation of Nrf2 antioxidant pathway.