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通过恢复肠道黏膜屏障和调节制瘤素M/制瘤素M受体途径来预防葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎。

Protects Against Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Restoring the Intestinal Mucosal Barrier and Modulating the Oncostatin M/Oncostatin M Receptor Pathway.

作者信息

Li Yao, Yang Xu, Yuan Jia-Ni, Lin Rui, Tian Yun-Yuan, Li Yu-Xin, Zhang Yan, Wang Xu-Fang, Xie Yan-Hua, Wang Si-Wang, Zheng Xiao-Hui

机构信息

The College of Life Sciences, Northwest University, Xi'an, China.

Air Force Hospital of Western Theater Command, Chengdu, China.

出版信息

Front Pharmacol. 2022 May 13;13:819826. doi: 10.3389/fphar.2022.819826. eCollection 2022.

Abstract

(IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.

摘要

(IR)是一种用于胃溃疡和十二指肠溃疡临床治疗的中药;然而,IR对溃疡性结肠炎(UC)的作用及其潜在机制尚不清楚。本研究探讨了IR对葡聚糖硫酸钠(DSS)诱导的UC小鼠的治疗作用及其潜在机制。采用超高效液相色谱-四极杆飞行时间质谱法分析IR的主要成分。然后,通过给予2.0% DSS 7天,随后给予2周自来水,共三个周期,建立UC小鼠模型,并给予IR。在第56天,评估小鼠的疾病活动指数(DAI)、结肠长度、病理变化和结肠组织的炎症反应。检测结肠组织的氧化应激和细胞凋亡,评估肠黏膜屏障的完整性,以评价IR的作用。此外,使用小鼠模型和Caco2细胞模型评估抑瘤素M(OSM)及其受体(OSMR)与IR治疗UC之间的关系。结果显示,IR显著减轻UC症状,包括挽救缩短的结肠长度;降低DAI评分、血清髓过氧化物酶和脂多糖水平、病理损伤、炎症细胞浸润以及结肠组织中白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6的mRNA水平;通过降低kelch样ECH相关蛋白1表达,增加核因子-红细胞2相关因子2和血红素加氧酶-1蛋白表达,减轻氧化应激和细胞凋亡;促进上皮细胞再生。IR还促进肠黏膜屏障的恢复,并调节OSM/OSMR途径以减轻UC。研究发现,IR通过恢复肠黏膜屏障和调节OSM/OSMR途径对UC发挥治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3793/9140055/2320020a9f46/fphar-13-819826-g001.jpg

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