肠黏膜机械屏障与肠易激综合征的关系
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摘要
肠易激综合征作为胃肠疾患的常见病,其发病机制与肠黏膜屏障、胃肠动力、内脏敏感性、脑-肠-菌轴等密切相关。其中肠黏膜机械屏障作为肠黏膜屏障最基础、最重要的屏障,近年来,对此开展的研究相对较多。肠黏膜机械屏障同肠黏膜化学、肠黏膜生物、肠黏膜免疫屏障构成肠黏膜屏障,共同抵御内毒素、病原菌等有害物质,维持肠道内环境稳态。肠黏膜机械屏障由肠黏膜上皮细胞、黏液层、紧密连接结构共同构成,任一环节异常,均会造成黏膜破坏,导致肠易激综合征。本文主要就肠黏膜机械屏障与肠易激综合征的关系做一综述,以期为临床实验提供思考方向与理论支持。
Irritable bowel syndrome is a common disease in gastrointestinal diseases, and its pathogenesis is closely related to intestinal mucosal barrier, gastrointestinal motility, visceral sensitivity, brain-gut-bacterial axis and so on. The intestinal mucosal mechanical barrier is the most important barrier for intestinal mucosa, and it has been studied comparatively in recent years.Intestinal mucosal mechanical barrier, Intestinal mucosal chemical barrier, intestinal mucosal biological barrier, intestinal mucosal immune barrier are consist of intestinal mucosal barrier, jointly resist bacterial endotoxin, pathogenic bacteria and other harmful substances, maintaining the homeostasis. Intestinal mucosal mechanical barrier is composed of intestinal mucosal epithelial cells,mucous layer and tight junction. Any abnormality in any link can cause the mucous membrane damage, leading to irritable bowel syndrome. In this paper, the relationship between intestinal mucosal mechanical barrier and irritable bowel syndrome is reviewed in order to provide the theoretical support for clinical trials.
Irritable bowel syndrome is a common disease in gastrointestinal diseases, and its pathogenesis is closely related to intestinal mucosal barrier, gastrointestinal motility, visceral sensitivity, brain-gut-bacterial axis and so on. The intestinal mucosal mechanical barrier is the most important barrier for intestinal mucosa, and it has been studied comparatively in recent years.Intestinal mucosal mechanical barrier, Intestinal mucosal chemical barrier, intestinal mucosal biological barrier, intestinal mucosal immune barrier are consist of intestinal mucosal barrier, jointly resist bacterial endotoxin, pathogenic bacteria and other harmful substances, maintaining the homeostasis. Intestinal mucosal mechanical barrier is composed of intestinal mucosal epithelial cells,mucous layer and tight junction. Any abnormality in any link can cause the mucous membrane damage, leading to irritable bowel syndrome. In this paper, the relationship between intestinal mucosal mechanical barrier and irritable bowel syndrome is reviewed in order to provide the theoretical support for clinical trials.
引文
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[14]Kudryashova E,Quintyn R,Seveau S,et al.Human defensins facilitate local unfolding of thermodynamically unstable regions of bacterial protein toxins[J].Immunity,2014,41(5):709-721.
[15]Sperandio B,Fischer N,Sansonetti P J.Mucosal physical and chemical innate barriers:Lessons from microbial evasion strategies[J].Seminars in Immunology,2015,27(2):111.
[16]Ambort D,Johansson M E V,Gustafsson J K,et al.Calcium and p H-dependent packing and release of the gel-forming MUC2 mucin[J].Proceedings of the National Academy of Sciences,2012,109(15):5645-5650.
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[18]Gustafsson J K,Ermund A,Johansson M E,et al.An ex vivo method for studying mucus formation,properties,and thickness in human colonic biopsies and mouse small and large intestinal explants[J].American Journal of Physiology Gastrointestinal&Liver Physiology,2011,302(4):G430.
[19]Larsson J M,Karlsson H,Crespo J G,et al.Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation[J].Inflammatory Bowel Diseases,2011,17(11):2299-2307.
[20]Birchenough G MH,Johansson ME,Gustafsson J K,et al.Newdevelopments in goblet cell mucus secretion and function[J].Mucosal Immunology,2015,8(4):712-719.
[21]Round A N,Rigby N M,Garcia d l T A,et al.Lamellar structures of MUC2-rich mucin:a potential role in governing the barrier and lubricating functions of intestinal mucus[J].Biomacromolecules,2012,13(10):3253-61.
[22]Dharmani P,Srivastava V,Kissoonsingh V,et al.Role of intestinal mucins in innate host defense mechanisms against pathogens[J].Journal of Innate Immunity,2009,1(2):123-135.
[23]Antoni L,Nuding S,Wehkamp J,et al.Intestinal barrier in inflammatory bowel disease[J].World Journal of Gastroenterology,2014,20(5):1165.
[24]Bergstrom K S,Kissoon-Singh V,Gibson D L,et al.Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa[J].Plos Pathogens,2010,6(5):e1000902.
[25]Johansson M E V,Phillipson M,Petersson J,et al.The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria[J].Gut Microbes,2010,105(39):51-54.
[26]Shan M,Gentile M,Yeiser J R,et al.Mucus Enhances Gut Homeostasis and Oral Tolerance by Delivering Immunoregulatory Signals[J].Science,2013,342(6157):447.
[27]Johansson M E V,Gustafsson J K,Holménlarsson J,et al.Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis[J].2014,63(2):281-291.
[28]Terry S,Nie M,Matter K,Balda MS.Rho signaling and tight junction functions.Physiology(Bethesda)2010(25):16-26
[29]邹仲之.组织学与胚胎学[M].6版.北京:人民卫生出版社,2005:15-18.
[30]Alsadi R,Khatib K,Guo S,et al.Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier[J].American Journal of PhysiologyGastrointestinal and Liver Physiology,2011,300(6):G1054-G1064.
[31]Ara N,Iijima K,Asanuma K,et al.Disruption of gastric barrier function by luminal nitrosative stress:a potential chemical insult to the human gastro-oesophageal junction[J].Gut,2008,57(3):306-313.
[32]Chen ML,Ge Z,Fox JG,et al.Disruption of tight junctions and induction of proinflammatory cytokine responses in colonic epithelial cells by Campylobacter jejuni[J].Infection and Immunity,2006,74(12):6581-6589.
[33]Hirano J,Yoshida T,Sugiyama T,et al.The effect of Lactobacillus rhamnosus on enterohemorrhagic Escherichia coli infection of human intestinal cells in vitro[J].Microbiology&Immunology,2003,47(6):405-409.
[34]孙兆瑞,刘红梅,杨志洲,等.肠三叶因子介导PI3K/Akt信号通路保护胃黏膜上皮细胞紧密连接[J].临床急诊杂志,2014,15(7):379-382,386.
[35]Bazzoni G.The JAMfamily of junctional adhesion molecules[J].Curr Opin Cell Biol 2003(15):525-530.
[36]Ulluwishewa D,Anderson RC,Mc Nabb WC,et al.Regulation of tight junction permeability by intestinal bacteria and dietary components[J].Journal of Nutrition,2011,141(5):769-776.
[37]Furuse M,Hata M,Furuse K,et al.Claudin-based tight junctions are crucial for the mammalian epidermal barrier:a lesson from claudin-1-deficient mice[J].Journal of Cell Biology,2002,156(6):1099-1111.
[38]Zhou Q,Zhang B,Verne G N.Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome[J].Pain,2009,136(5):41.
[39]Goulet O,Ruemmele F F,Colomb V.Irreversible intestinal failure[J].Journal of Pediatric Gastroenterology&Nutrition,2004,38(3):250.
[40]Polimeno L,Loiacono M,Pesetti B,et al.Anisakiasis,an underestimated infection:effect on intestinal permeability of Anisakis simplex-sensitized patients[J].Foodborne Pathogens&Disease,2010,7(7):809.
[41]Wang W,Uzzau S,Goldblum S E,et al.Human zonulin,a potential modulator of intestinal tight junctions[J].Journal of Cell Science,2000,113 Pt 24(113 Pt 24):4435.
[42]Laukoetter MG,Nava P,Lee W Y,et al.JAMA regulates permeability and inflammation in the intestine in vivo[J].Journal of Experimental Medicine,2007,204(13):3067.
[43]Su L,Shen L D,Nalle S,et al.Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis[J].Gastroenterology,2009,136(2):551-563.
[44]徐万里,陆高,梁世杰,等.短链脂肪酸介导的菌群-宿主互动与肠易激综合征的研究进展[J].世界华人消化杂志,2015(36):5815-5822.
[2]彭珊,赵钢,李春艳.肠易激综合征的发病机制研究进展[J].中国医药导报,2016,13(6):54-57.
[3]Young-Eun J.Increased Expression of Brain-derived Neurotrophic Factor in Irritable Bowel Syndrome and Its Correlation With Abdominal Pain[J].Journal of Neurogastroenterology&Motility,2013,19(19):109-111.
[4]Sohn W,Lee O Y,Lee S P,et al.Mast cell number,substance P and vasoactive intestinal peptide in irritable bowel syndrome with diarrhea[J].Scandinavian Journal of Gastroenterology,2014,49(1):43.
[5]Mccauley H A,Guasch G.Three cheers for the goblet cell:maintaining homeostasis in mucosal epithelia[J].Trends in Molecular Medicine,2015,21(8):492-503.
[6]高英茂,李和.组织学与胚胎学[M].2版.北京:人民卫生出版社,2010.
[7]常建星,陈双,蒋龙元,等.小肠杯状细胞在大鼠休克后肠黏膜重建中的作用[J].中华胃肠外科杂志,2005,8(6):510-512.
[8]Mcdole J R,Wheeler L W,Mcdonald K G,et al.Goblet cells deliver luminal antigen to CD103+DCs in the small intestine[J].Nature,2012,483(7389):345-349.
[9]Salzman N H,Hung K,Haribhai D,et al.Enteric defensins are essential regulators of intestinal microbial ecology[J].Nature Immunology,2010,11(1):76-83.
[10]Stromberg R,Ottosson H,Miraglia E,et al.Boosting Innate Immunity with New Potent Inducers of Antimicrobial Peptide Expression[J].Meeting of the Scandinanan-society-for-immunology 2014:432.
[11]Zaragoza M M,Sankaran-Walters S,Canfield D R,et al.Persistence of gut mucosal innate immune defenses by entericα-defensin expression in the simian immunodeficiency virus model of AIDS[J].Journal of Immunology,2011,186(3):1589.
[12]Cole J N,Nizet V.Bacterial Evasion of Host Antimicrobial Peptide Defenses[J].Microbiol Spectr,2016,4(1).
[13]Bevins C L,Martinporter E,Ganz T.Defensins and innate host defence of the gastrointestinal tract[J].Gut,1999,45(6):911-5.
[14]Kudryashova E,Quintyn R,Seveau S,et al.Human defensins facilitate local unfolding of thermodynamically unstable regions of bacterial protein toxins[J].Immunity,2014,41(5):709-721.
[15]Sperandio B,Fischer N,Sansonetti P J.Mucosal physical and chemical innate barriers:Lessons from microbial evasion strategies[J].Seminars in Immunology,2015,27(2):111.
[16]Ambort D,Johansson M E V,Gustafsson J K,et al.Calcium and p H-dependent packing and release of the gel-forming MUC2 mucin[J].Proceedings of the National Academy of Sciences,2012,109(15):5645-5650.
[17]Johansson M E V,Sj觟vall H,Hansson G C.The gastrointestinal mucus system in health and disease[J].Nature Reviews Gastroenterology&Hepatology,2013,10(6):352.
[18]Gustafsson J K,Ermund A,Johansson M E,et al.An ex vivo method for studying mucus formation,properties,and thickness in human colonic biopsies and mouse small and large intestinal explants[J].American Journal of Physiology Gastrointestinal&Liver Physiology,2011,302(4):G430.
[19]Larsson J M,Karlsson H,Crespo J G,et al.Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation[J].Inflammatory Bowel Diseases,2011,17(11):2299-2307.
[20]Birchenough G MH,Johansson ME,Gustafsson J K,et al.Newdevelopments in goblet cell mucus secretion and function[J].Mucosal Immunology,2015,8(4):712-719.
[21]Round A N,Rigby N M,Garcia d l T A,et al.Lamellar structures of MUC2-rich mucin:a potential role in governing the barrier and lubricating functions of intestinal mucus[J].Biomacromolecules,2012,13(10):3253-61.
[22]Dharmani P,Srivastava V,Kissoonsingh V,et al.Role of intestinal mucins in innate host defense mechanisms against pathogens[J].Journal of Innate Immunity,2009,1(2):123-135.
[23]Antoni L,Nuding S,Wehkamp J,et al.Intestinal barrier in inflammatory bowel disease[J].World Journal of Gastroenterology,2014,20(5):1165.
[24]Bergstrom K S,Kissoon-Singh V,Gibson D L,et al.Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa[J].Plos Pathogens,2010,6(5):e1000902.
[25]Johansson M E V,Phillipson M,Petersson J,et al.The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria[J].Gut Microbes,2010,105(39):51-54.
[26]Shan M,Gentile M,Yeiser J R,et al.Mucus Enhances Gut Homeostasis and Oral Tolerance by Delivering Immunoregulatory Signals[J].Science,2013,342(6157):447.
[27]Johansson M E V,Gustafsson J K,Holménlarsson J,et al.Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis[J].2014,63(2):281-291.
[28]Terry S,Nie M,Matter K,Balda MS.Rho signaling and tight junction functions.Physiology(Bethesda)2010(25):16-26
[29]邹仲之.组织学与胚胎学[M].6版.北京:人民卫生出版社,2005:15-18.
[30]Alsadi R,Khatib K,Guo S,et al.Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier[J].American Journal of PhysiologyGastrointestinal and Liver Physiology,2011,300(6):G1054-G1064.
[31]Ara N,Iijima K,Asanuma K,et al.Disruption of gastric barrier function by luminal nitrosative stress:a potential chemical insult to the human gastro-oesophageal junction[J].Gut,2008,57(3):306-313.
[32]Chen ML,Ge Z,Fox JG,et al.Disruption of tight junctions and induction of proinflammatory cytokine responses in colonic epithelial cells by Campylobacter jejuni[J].Infection and Immunity,2006,74(12):6581-6589.
[33]Hirano J,Yoshida T,Sugiyama T,et al.The effect of Lactobacillus rhamnosus on enterohemorrhagic Escherichia coli infection of human intestinal cells in vitro[J].Microbiology&Immunology,2003,47(6):405-409.
[34]孙兆瑞,刘红梅,杨志洲,等.肠三叶因子介导PI3K/Akt信号通路保护胃黏膜上皮细胞紧密连接[J].临床急诊杂志,2014,15(7):379-382,386.
[35]Bazzoni G.The JAMfamily of junctional adhesion molecules[J].Curr Opin Cell Biol 2003(15):525-530.
[36]Ulluwishewa D,Anderson RC,Mc Nabb WC,et al.Regulation of tight junction permeability by intestinal bacteria and dietary components[J].Journal of Nutrition,2011,141(5):769-776.
[37]Furuse M,Hata M,Furuse K,et al.Claudin-based tight junctions are crucial for the mammalian epidermal barrier:a lesson from claudin-1-deficient mice[J].Journal of Cell Biology,2002,156(6):1099-1111.
[38]Zhou Q,Zhang B,Verne G N.Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome[J].Pain,2009,136(5):41.
[39]Goulet O,Ruemmele F F,Colomb V.Irreversible intestinal failure[J].Journal of Pediatric Gastroenterology&Nutrition,2004,38(3):250.
[40]Polimeno L,Loiacono M,Pesetti B,et al.Anisakiasis,an underestimated infection:effect on intestinal permeability of Anisakis simplex-sensitized patients[J].Foodborne Pathogens&Disease,2010,7(7):809.
[41]Wang W,Uzzau S,Goldblum S E,et al.Human zonulin,a potential modulator of intestinal tight junctions[J].Journal of Cell Science,2000,113 Pt 24(113 Pt 24):4435.
[42]Laukoetter MG,Nava P,Lee W Y,et al.JAMA regulates permeability and inflammation in the intestine in vivo[J].Journal of Experimental Medicine,2007,204(13):3067.
[43]Su L,Shen L D,Nalle S,et al.Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis[J].Gastroenterology,2009,136(2):551-563.
[44]徐万里,陆高,梁世杰,等.短链脂肪酸介导的菌群-宿主互动与肠易激综合征的研究进展[J].世界华人消化杂志,2015(36):5815-5822.