>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
脱氧胆酸促进肠道组织产生IL-1β及诱导肠道炎症作用的研究
作者:赵胜男1 2  龚自珍1 2  周洁菲1 2  吴瑾1 2 
单位:1. 上海交通大学医学院附属新华医院, 上海 200092;
2. 上海市儿科医学研究所, 上海 200092
关键词:炎症性肠病 脱氧胆酸 白细胞介素1β 炎症小体 小鼠 
分类号:R574.62
出版年·卷·期(页码):2017·36·第二期(171-176)
摘要:

目的:研究高脱氧胆酸(DCA)对肠道促炎因子IL-1β等的表达及肠道炎症的诱导作用。方法:给予小鼠添加DCA的膳食,建立小鼠肠道高DCA模型,采用HE染色观察小鼠肠道病理损伤情况;以Western Blot检测结肠组织成熟IL-1β的产生;以实时PCR检测IL-6、MCP-1的表达水平;通过髓过氧化物酶(MPO)活力检测肠道炎症情况。结果:给予小鼠添加0.2% DCA的膳食3个月后,其结肠长度明显缩短[对照组(8.1±0.5)cm vs DCA组(7.3±0.3)cm,P<0.01];代表肠道炎症程度的指标MPO活性显著上升[对照组(1.6±0.4)U·g-1 vs DCA组(3.0±0.5)U·g-1P<0.01];HE染色可见结肠黏膜破损,黏膜下水肿及炎症细胞浸润。同时DCA膳食可明显诱导结肠组织成熟IL-1β的产生,并导致促炎因子IL-6(对照组1.0±0.1 vs DCA组174.6±45.9,P<0.01)及髓系趋化因子MCP-1(对照组1.0±0.1 vs DCA组187.8±26.2,P<0.001)的mRNA水平表达显著升高。结论:高水平DCA可诱导肠道炎症发生,激活炎症小体、促进成熟IL-1β产生可能是其重要作用机制之一。

Objective: To investigate the effect of high level deoxycholic acid(DCA)on the IL-1β production and intestinal inflammation occurrence. Methods: Mice were fed with routine diet supplemented with 0.2% DCA, HE staining was performed to observe intestinal pathological injury; Western Blot and Realtime PCR were adopted to detect mature IL-1β production and IL-6, MCP-1 expression respectively; intestinal inflammation was assessed by the measurement of MPO activity. Results: Mice fed the DCA-supplemented diet developed obvious intestinal inflammation and injury, as evidenced by significant shortening of colon length [control group(8.1±0.5) cm vs DCA group(7.3±0.3)cm,P<0.01] and much higher MPO activity [control group(1.6±0.4)U·g-1 vs DCA group(3.0±0.5)U·g-1,P<0.01]; HE staining of colonic tissue in DCA group showed intestinal mucosal impairment, submucosal edema and inflammatory cell infiltration. Of note, the mature IL-1β level in colon tissue was elevated dramatically in DCA-fed group. Meanwhile, the mRNA levels of IL-6 (control group 1.0±0.1 vs DCA group 174.6±45.9,P<0.01) and MCP-1 (control group 1.0±0.1 vs DCA group 187.8±26.2,P<0.001) in DCA group were significantly increased as well. Conclusion: High level DCA can induce the occurrence of intestinal inflammation, which may at least partially depend on the activation of inflammasome and production of IL-1β.

参考文献:

[1] 张丽,陈洪,王玉连.人类炎症性肠病的microRNA表达分析研究的meta分析[J].现代医学,2016,44(3):306-315.
[2] KAPLAN G G.The global burden of IBD:from 2015 to 2025[J].Nat Rev Gastroenterol Hepatol,2015,12(12):720-727.
[3] FROLKIS A,DIELEMAN L A,BARKEMA H W,et al.Environment and the inflammatory bowel diseases[J].Can J Gastroenterol,2013,27(3):e18-e24.
[4] STENMAN L K,HOLMA R,KORPELA R.High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids[J].World J Gastroenterol,2012,18(9):923-929.
[5] RAIMONDI F,SANTORO P,BARONE M V,et al.Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation[J].Am J Physiol Gastrointest Liver Physiol,2008,294(4):G906-G913.
[6] BERNSTEIN H,HOLUBEC H,BERNSTEIN C,et al.Unique dietary-related mouse model of colitis[J].Inflamm Bowel Dis,2006,12(4):278-293.
[7] BAUER C,DUEWELL P,MAYER C,et al.Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome[J].Gut,2010,59(9):1192-1199.
[8] SIEGMUND B,LEHR H A,FANTUZZI G,et al.IL-1 beta-converting enzyme (caspase-1) in intestinal inflammation[J].Proc Natl Acad Sci U S A,2001,98(23):13249-13254.
[9] SCHRODER K,TSCHOPP J.The inflammasomes[J].Cell,2010,140(6):821-832.
[10] COCCIA M,HARRISON O J,SCHIERING C,et al.IL-1beta mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells[J].J Exp Med,2012,209(9):1595-1609.
[11] PAVLIDIS P,POWELL N,VINCENT R P,et al.Systematic review:bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence?[J].Aliment Pharmacol Ther,2015,42(7):802-817.
[12] ALBERTS D S,EINSPAHR J G,EARNEST D L,et al.Fecal bile acid concentrations in a subpopulation of the wheat bran fiber colon polyp trial[J].Cancer Epidemiol Biomarkers Prev,2003,12(3):197-200.
[13] TRAUB R J,TANG B,JI Y,et al.A rat model of chronic postinflammatory visceral pain induced by deoxycholic acid[J].Gastroenterology,2008,135(6):2075-2083.
[14] CASTRO J,OCAMPO Y,FRANCO L.Cape gooseberry [Physalis peruviana L.] calyces ameliorate TNBS acid-induced colitis in rats[J].J Crohns Colitis,2015,9(11):1004-1015.
[15] KEATING N,KEELY S J.Bile acids in regulation of intestinal physiology[J].Curr Gastroenterol Rep,2009,11(5):375-382.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 250346 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364