切换至 "中华医学电子期刊资源库"

中华临床医师杂志(电子版) ›› 2020, Vol. 14 ›› Issue (09) : 735 -739. doi: 10.3877/cma.j.issn.1674-0785.2020.09.014

所属专题: 文献

综述

肠黏膜屏障功能及损伤机制研究进展
牛鹏飞1, 王延召1, 曾庆敏1, 雷福明1,()   
  1. 1. 100144 北京大学首钢医院胃肠外科
  • 收稿日期:2020-03-10 出版日期:2020-09-15
  • 通信作者: 雷福明

Progress in research of intestinal mucosal barrier function and its dysfunction mechanisms

Pengfei Niu1, Yanzhao Wang1, Qingmin Zeng1, Fuming Lei1,()   

  1. 1. Department of Gastrointestinal Surgery, Shougang Hospital, Peking University, Beijing 100144, China
  • Received:2020-03-10 Published:2020-09-15
  • Corresponding author: Fuming Lei
  • About author:
    Corresponding author: Lei Fuming, Email:
引用本文:

牛鹏飞, 王延召, 曾庆敏, 雷福明. 肠黏膜屏障功能及损伤机制研究进展[J]. 中华临床医师杂志(电子版), 2020, 14(09): 735-739.

Pengfei Niu, Yanzhao Wang, Qingmin Zeng, Fuming Lei. Progress in research of intestinal mucosal barrier function and its dysfunction mechanisms[J]. Chinese Journal of Clinicians(Electronic Edition), 2020, 14(09): 735-739.

肠黏膜屏障由肠上皮细胞和细胞外成分共同组成,具有结构复杂和功能多样的特点。肠黏膜屏障以动态变化的形式,在机体消化过程中选择性地吸收水和营养物质、阻止肠道细菌异位、发挥肠道免疫功能,以协助机体维持肠道的完整性和免疫稳态。导致肠黏膜屏障功能紊乱的病因如慢性炎症、菌群失调、环境因素改变等,可独立或协同引发生化级联反应,导致慢性炎症的发生,进一步可导致多种肠道疾病如炎症性肠病、肠易激综合征、结肠恶性肿瘤以及一部分肠外疾病(如慢性非酒精性肝病、1型糖尿病、肥胖等)。了解肠黏膜屏障的损伤机制,对于研究肠道疾病或肠外相关疾病具有重要意义。

The intestinal mucosal barrier is composed of intestinal epithelial cells and extracellular components, which has the characteristics of complex structure and diverse functions. In the form of dynamic changes, the intestinal mucosa barrier selectively absorbs water and nutrients, prevents intestinal bacterial translocation, and has intestinal immune function in the process of digestion, so as to help the body maintain the integrity of the intestinal tract and immune homeostasis. The causes of intestinal mucosal barrier dysfunction, such as chronic inflammation, dysbacteriosis, and changes in environmental factors, can independently or collaboratively cause biochemical cascade reactions, leading to the occurrence of chronic inflammation and a variety of intestinal diseases, such as inflammatory bowel disease, irritable bowel syndrome, colonic cancer, and some extraintestinal diseases (such as chronic nonalcoholic liver disease, type I diabetes, and obesity). It is of great significance to understand the mechanism of intestinal mucosal barrier dysfunction for the study of intestinal diseases or extraintestinal related diseases.

1
Turner JR. Intestinal mucosal barrier function in health and disease [J]. Nat Rev Immunol, 2009, 9(11): 799-809.
2
Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease [J]. Expert Rev Gastroenterol Hepatol, 2017, 11(9): 821-834.
3
Nalle SC, Turner JR. Intestinal barrier loss as a critical pathogenic link between inflammatory bowel disease and graft-versus-host disease [J]. Mucosal Immunol, 2015, 8(4): 720-30.
4
Nagpal R, Yadav H. Bacterial Translocation from the gut to the distant organs: an overview [J]. Ann Nutr Metab, 2017, 71 Suppl 1: 11-16.
5
Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens [J]. Nat Rev Immunol, 2003, 3(4): 331-341.
6
黎介寿. 肠衰竭—概念、营养支持与肠粘膜屏障维护 [J]. 中国临床营养杂志, 2004, 12(3): 155-8.
7
Kurashima Y, Kiyono H. Mucosal ecological network of epithelium and immune cells for gut homeostasis and tissue healing [J]. Annu Rev Immunol, 2017, 35: 119-147.
8
Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis [J]. J Allergy Clin Immunol, 2009, 124(1): 3-20; quiz 1-2.
9
Edelblum KL, Turner JR. The tight junction in inflammatory disease: communication breakdown [J]. Curr Opin Pharmacol, 2009, 9(6): 715-720.

URL    
10
Fuladi S, Jannat RW, Shen L, et al. Computational Modeling of Claudin Structure and Function [J]. Int J Mol Sci, 2020, 21(3): 742.
11
Jin Y, Ibrahim D, Magness ST, et al. Knockout of ClC-2 reveals critical functions of adherens junctions in colonic homeostasis and tumorigenicity [J]. Am J Physiol Gastrointest Liver Physiol, 2018, 315(6): G966-G979.
12
Salvo Romero E, Alonso Cotoner C, Pardo Camacho C, et al. The intestinal barrier function and its involvement in digestive disease [J]. Rev Esp Enferm Dig, 2015, 107(11): 686-696.
13
Kojima T, Murata M, Go M, et al. Connexins induce and maintain tight junctions in epithelial cells [J]. J Membr Biol, 2007, 217(1-3): 13-19.
14
Johansson MEV, Larsson JMH, Hansson GC. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions [J]. Proc Natl Acad Sci USA, 2011, 108 (Suppl 1): 4659-4665.
15
Pelaseyed T, Bergstrom JH, Gustafsson JK, et al. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system [J]. Immunol Rev, 2014, 260(1): 8-20.
16
Muniz LR, Knosp C, Yeretssian G. Intestinal antimicrobial peptides during homeostasis, infection, and disease [J]. Front Immunol, 2012, 3: 310.
17
Chairatana P, Nolan EM. Defensins, lectins, mucins, and secretory immunoglobulin A: microbe-binding biomolecules that contribute to mucosal immunity in the human gut [J]. Crit Rev Biochem Mol Biol, 2017, 52(1): 45-56.
18
Cerutti A, Rescigno M. The biology of intestinal immunoglobulin A responses [J]. Immunity, 2008, 28(6): 740-750.

URL    
19
Corr SC, Gahan CC, Hill C. M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis [J]. FEMS Immunol Med Microbiol, 2008, 52(1): 2-12.
20
Gill N, Wlodarska M, Finlay BB. Roadblocks in the gut: barriers to enteric infection [J]. Cell Microbiol, 2011, 13(5): 660-669.

URL    
21
Castoldi A, Favero de Aguiar C, Moraes-Vieira PM, et al. They must hold tight: junction proteins, microbiota and immunity in intestinal mucosa [J]. Curr Protein Pept Sci, 2015, 16(7): 655-671.
22
Takiishi T, Fenero CIM, Câmara NOS. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life [J]. Tissue Barriers, 2017, 5(4): e1373208.
23
Schroeder BO. Fight them or feed them: how the intestinal mucus layer manages the gut microbiota [J]. Gastroenterol Rep (Oxf), 2019, 7(1): 3-12.
24
Haussner F, Chakraborty S, Halbgebauer R, et al. Challenge to the Intestinal Mucosa During Sepsis [J]. Front Immunol, 2019, 10: 891.
25
Wells JM, Brummer RJ, Derrien M, et al. Homeostasis of the gut barrier and potential biomarkers [J]. Am J Physiol Gastrointest Liver Physiol, 2017, 312(3): G171-G193.
26
Kanoore edul VS, Dubin A, Ince C. The microcirculation as a therapeutic target in the treatment of sepsis and shock [J]. Semin Respir Crit Care Med, 2011, 32(5): 558-568.
27
Wang L, Bastarache JA, Ware LB. The coagulation cascade in sepsis [J]. Curr Pharm Des, 2008, 14(19): 1860-1869.
28
Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response [J]. Curr Opin Crit Care, 2011, 17(2): 153-159.

URL    
29
Defazio J, Fleming ID, Shakhsheer B, et al. The opposing forces of the intestinal microbiome and the emerging pathobiome [J]. Surg Clin North Am, 2014, 94(6): 1151-1161.
30
Jiang LY, Zhang M, Zhou TE, et al. Changes of the immunological barrier of intestinal mucosa in rats with sepsis [J]. World J Emerg Med, 2010, 1(2): 138-143.
31
Chang RM, Wen LQ, Chang JX, et al. Repair of damaged intestinal mucosa in a mouse model of sepsis [J]. World J Emerg Med, 2013, 4(3): 223-228.
32
Farooq PD, Urrunaga NH, Tang DM, et al. Pseudomembranous colitis [J]. Dis Mon, 2015, 61(5): 181-206.
33
Rodriguez C, Taminiau B, Van broeck J, et al. Clostridium difficile infection and intestinal microbiota interactions [J]. Microb Pathog, 2015, 89: 201-209.
34
Fachi JL, Felipe JS, Pral LP, et al. Butyrate protects mice from clostridium difficile-induced colitis through an HIF-1-dependent mechanism [J]. Cell Rep, 2019, 27(3): 750-761, e7.
35
Buffie CG, Bucci V, Stein RR, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile [J]. Nature, 2015, 517(7533): 205-208.
36
Schubert AM, Rogers MAM, Ring C, et al. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls [J]. mBio, 2014, 5(3): e01021-14.
37
Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile [J]. N Engl J Med, 2013, 368(5): 407-415.
38
Podolsky DK. Inflammatory bowel disease (1) [J]. N Engl J Med, 1991, 325(13): 928-037.
39
Ventham NT, Kennedy NA, Nimmo ER, et al. Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics [J]. Gastroenterology, 2013, 145(2): 293-308.

URL    
40
Grill JI, Neumann J, Hiltwein F, et al. Intestinal E-cadherin deficiency aggravates dextran sodium sulfate-induced colitis [J]. Dig Dis Sci, 2015, 60(4): 895-902.
41
Tanaka H, Takechi M, Kiyonari H, et al. Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice [J]. Gut, 2015, 64(10): 1529-1538.
42
Laukoetter MG, Nava P, Lee WY, et al. JAM-A regulates permeability and inflammation in the intestine in vivo [J]. J Exp Med, 2007, 204(13): 3067-3076.
43
Vetrano S, Rescigno M, Cera MR, et al. Unique role of junctional adhesion molecule-a in maintaining mucosal homeostasis in inflammatory bowel disease [J]. Gastroenterology, 2008, 135(1): 173-184.
44
Wang F, Graham WV, Wang Y, et al. Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression [J]. Am J Pathol, 2005, 166(2): 409-419.
45
Suenaert P, Bulteel V, Lemmens L, et al. Anti-tumor necrosis factor treatment restores the gut barrier in Crohn′s disease [J]. Am J Gastroenterol, 2002, 97(8): 2000-2004.
46
Allais L, Kerckhof FM, Verschuere S, et al. Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut [J]. Environ Microbiol, 2016, 18(5): 1352-1363.
47
Fricker M, Goggins BJ, Mateer S, et al. Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction [J]. JCI Insight, 2018, 3(3): pii 94040.
48
Bull-Otterson L, Feng W, Kirpich I, et al. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment [J]. PLoS One, 2013, 8(1): e53028.
49
Fleming S, Toratani S, Shea-Donohue T, et al. Pro- and anti-inflammatory gene expression in the murine small intestine and liver after chronic exposure to alcohol [J]. Alcohol Clin Exp Res, 2001, 25(4): 579-589.
50
Malaguarnera G, Giordano M, Nunnari G, et al. Gut microbiota in alcoholic liver disease: pathogenetic role and therapeutic perspectives [J]. World J Gastroenterol, 2014, 20(44): 16639-16648.
51
Wang DQ, Carey MC. Therapeutic uses of animal biles in traditional Chinese medicine: an ethnopharmacological, biophysical chemical and medicinal review [J]. World J Gastroenterol, 2014, 20(29): 9952-9975.
52
Hegyi P, Maleth J, Walters JR, et al. Guts and gall: bile acids in regulation of intestinal epithelial function in health and disease [J]. Physiol Rev, 2018, 98(4): 1983-2023.
53
Merchant NB, Rogers CM, Trivedi B, et al. Ligand-dependent activation of the epidermal growth factor receptor by secondary bile acids in polarizing colon cancer cells [J]. Surgery, 2005, 138(3): 415-421.
54
Raimondi F, Santoro P, Barone MV, 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.
55
König J, Wells J, Cani PD, et al. Human Intestinal Barrier Function in Health and Disease [J]. Clin Transl Gastroenterol, 2016, 7(10): e196.
56
Vanuytsel T, Van Wanrooy S, Vanheel H, et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism [J]. Gut, 2014, 63(8): 1293-1299.

URL    
57
Rodiño-Janeiro BK, Alonso-Cotoner C, Pigrau M, et al. Role of corticotropin-releasing factor in gastrointestinal permeability [J]. J Neurogastroenterol Motil, 2015, 21(1): 33-50.
58
Stevens BR, Goel R, Seungbum K, et al. Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression [J]. Gut, 2018, 67(8): 1555-1557.
[1] 林文, 王雨萱, 许嘉悦, 王矜群, 王睿娜, 何董源, 樊沛. 人工关节置换登记系统的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(06): 834-841.
[2] 卫杨文祥, 黄浩然, 刘予豪, 陈镇秋, 王海彬, 周驰. 股骨头坏死细胞治疗的前景和挑战[J]. 中华关节外科杂志(电子版), 2023, 17(05): 694-700.
[3] 占一姗, 朱友荣, 张守华, 陶强. 急性阑尾炎相关诊断预测模型的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(02): 151-154.
[4] 林华婵, 林赛娟, 陈民学. 腹横筋膜阻滞对老年斜疝患者麻醉效果及肠黏膜屏障功能的影响[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(04): 454-457.
[5] 乔雨晴, 沈磊, 周林香, 李湘杰, 严博. 结缔组织生长因子单克隆抗体对小鼠慢性结肠炎肠壁纤维化的作用[J]. 中华结直肠疾病电子杂志, 2023, 12(02): 125-131.
[6] 杨程鹏, 金佳, 王明祥, 戴光耀. 直肠黏膜环切联合阴道后壁折叠治疗出口梗阻型便秘的效果观察[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 471-474.
[7] 杨忠华, 马晓菡, 刁磊, 胡静, 陈熙. 双气囊小肠镜在小肠CT造影结果阴性患者中的诊断价值[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 475-479.
[8] 朱风尚, 舍玲, 丁永年, 杨长青. 警惕炎症性肠病与少见肠道疾病的鉴别诊断[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 273-276.
[9] 邱春华, 张志宏. 1108例小肠疾病的临床诊断及检查策略分析[J]. 中华临床医师杂志(电子版), 2023, 17(9): 948-954.
[10] 方辉, 李菲, 张帆, 魏强, 陈强谱. 外源性瘦素对梗阻性黄疸大鼠肠黏膜增殖的影响[J]. 中华临床医师杂志(电子版), 2023, 17(05): 575-580.
[11] 史亚东, 顾建平. 无症状肺栓塞的诊断与治疗进展[J]. 中华介入放射学电子杂志, 2023, 11(02): 155-158.
[12] 陈静, 逯艳艳, 徐耀东, 马颖才. 联动成像技术在肠道病变中的研究进展[J]. 中华胃肠内镜电子杂志, 2023, 10(03): 195-199.
[13] 王擎, 王冠峰, 陈星. 胃食管阀瓣的Hill分级在胃食管反流病中的应用价值[J]. 中华胃肠内镜电子杂志, 2023, 10(02): 125-130.
[14] 桑素娟, 王盈盈, 李丽楠, 刘晓冰, 雷燕妮, 程艳爽. 胃管抽吸物pH测试法用于胃管位置定位的研究进展[J]. 中华胃肠内镜电子杂志, 2023, 10(02): 131-135.
[15] 买买提·依斯热依力, 尹强, 尹海龙, 董雨微, 王永康, 克力木·阿不都热依木, 阿吉艾克拜尔·艾萨. 传统医药治疗胃食管反流病的研究进展[J]. 中华胃食管反流病电子杂志, 2023, 10(02): 100-104.
阅读次数
全文


摘要