Unconjugated bilirubin alleviates experimental ulcerative colitis by regulating intestinal barrier function and immune inflammation
Unconjugated bilirubin alleviates experimental ulcerative colitis by regulating intestinal barrier function and immune inflammation作者机构：Department of Biochemistry and Molecular BiologyHeilongjiang Provincial Science and Technology Innovation Team in Higher EducationInstitutes for Infection and Immunity Harbin Medical University GI Biopharma Inc. Department of General Surgery the Second Affiliated Hospital of Harbin Medical University
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2019年第25卷第15期
页 面：1865-1877页
核心收录：
学科分类：10[医学]
基 金：Supported by grants from the National Natural Foundation of China No.81703232
主 题：Ulcerative colitis Unconjugated bilirubin Intestinal barrier Intestinal homeostasis Digestive proteases Inflammation
摘 要：BACKGROUND Unconjugated bilirubin(UCB) is generally considered toxic but has gained recent prominence for its anti-inflammatory properties. However, the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain *** To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced *** Acute colitis was induced by 3%(w/v) dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d. Concurrently, mice with colitis were administered 0.2 mL UCB(400 μmol/L) by intra-gastric gavage for 7 *** activity index(DAI) was monitored daily. Mice were sacrificed at the end of the experiment. The length of the colon and weight of the spleen were recorded. Serum level of D-lactate, intestinal digestive proteases activity, and changes to the gut flora were analyzed. In addition, colonic specimens were analyzed by histology and for expression of inflammatory markers and *** Mice treated with UCB had significantly relieved severity of colitis, including lower DAI, longer colon length, and lower spleen weight(colon length: 4.92 ±0.09 cm vs 3.9 ± 0.15 cm; spleen weight: 0.33 ± 0.04 vs 0.74 ± 0.04, P 0.001). UCB administration inactivated digestive proteases(chymotrypsin: 18.70 ± 0.69 U/g vs44.81 ± 8.60 U/g; trypsin: 1.52 ± 0.23 U/g vs 9.05 ± 1.77 U/g, P 0.01), increased expression of tight junction(0.99 ± 0.05 vs 0.57 ± 0.03, P 0.001), decreased serum level of D-lactate(31.76 ± 3.37 μmol/L vs 54.25 ± 1.45 μmol/L, P 0.001), and lowered histopathological score(4 ± 0.57 vs 7 ± 0.57, P 0.001) and activity of myeloperoxidase(46.79 ± 2.57 U/g vs 110.32 ± 19.19 U/g, P 0.001). UCB also regulated the intestinal microbiota, inhibited expression of tumor necrosis factor(TNF) α and interleukin 1β(TNF-α: 52.61 ± 7.81 pg/mg vs 105.04 ± 11.92 pg/mg,interleukin 1β: 13.43 ± 1.68 vs 32.41 ± 4.62 pg/mg,
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