蛋白酶与自身消化在炎症性肠病发生机制中的作用与启示
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摘要
炎症性肠病(IBD)系原因未明的肠道非特异性炎性疾病,主要包括溃疡性结肠炎和克罗恩病。IBD与消化性溃疡(PUD)在临床表现、病理组织学改变与治疗策略方面均有相似之处,故胃蛋白酶在PUD的作用值得IBD借鉴。消化液中的消化酶(特别是胰蛋白酶)所致的"自身消化"在IBD的发生与发展中起着重要作用。文章重点阐述胰蛋白酶与自身消化导致的黏膜屏障损伤在IBD溃疡形成中的作用及临床意义,并提出消化道溃疡性疾病的新概念。
Inflammatory bowel diseases(IBD)are non-specific inflammatory diseases of unknown cause,mainly including ulcerative colitis and Crohn's disease. IBDs have some similarities to peptic ulcer diseases(PUD)in clinical manifestations,histopathological changes and treatment strategies,and therefore pepsin might have a similar effect on both PUD and IBD. Recent studies show that"self-digestion"induced by digestive enzymes,especially trypsin,may play an important role in the development and progression of IBD. This article focuses on the role of mucosal barrier injury induced by trypsin and self-digestion in the formation of digestive ulcer in IBD.
Inflammatory bowel diseases(IBD)are non-specific inflammatory diseases of unknown cause,mainly including ulcerative colitis and Crohn's disease. IBDs have some similarities to peptic ulcer diseases(PUD)in clinical manifestations,histopathological changes and treatment strategies,and therefore pepsin might have a similar effect on both PUD and IBD. Recent studies show that"self-digestion"induced by digestive enzymes,especially trypsin,may play an important role in the development and progression of IBD. This article focuses on the role of mucosal barrier injury induced by trypsin and self-digestion in the formation of digestive ulcer in IBD.
引文
[1]谢睿,李全朋,缪林.炎症性肠病免疫发病机制研究进展[J].医学研究生学报,2013,26(2):206-210.
[2]Magro F,Gionchetti P,Eliakim R,et al.Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis.Part1:Definitions,Diagnosis,Extra-intestinal Manifestations,Pregnancy,Cancer Surveillance,Surgery,and Ileo-anal Pouch Disorders[J].JCrohns Colitis,2017(2):649-670.
[3]冯军鹏,陈秀,王瑞玲,等.不同胃液中胃蛋白酶含量的测定[J].中国医学工程,2012(3):3-5.
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[5]Gaw AJ,Williams LV,Spraggs CF,et al.Role of pepsin in the development of indomethacin-induced antral ulceration in the rat[J].Aliment Pharm Ther,1995,9(2):167-172.
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[7]Henriksson A,Khaled AKD,Conway PL.The Effect of Caecectomy on the Faecal Concentrations of Urobilinogen and Active Trypsin in Mice[J].Microb Ecol Heal Dis,1996,9(2):61-65.
[8]Zhou J,Jiang M,Yang X,et al.Unconjugated bilirubin ameliorates the inflammation and digestive protease increase in TNBS-induced colitis[J].Mol Med Rep,2017(2):1779-1784.
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[10]Senda S,Fujiyama Y,Bamba T,et al.Treatment of ulcerative colitis with camostat mesilate,a serine protease inhibitor[J].Int Med,1993,32(4):350-354.
[11]Sakuraba A,Iwao Y,Matsuoka K,et al.Endoscopic and Pathologic Changes of the Upper Gastrointestinal Tract in Crohn's Disease[J].Biomed Res Int,2014,Article ID610767.
[12]Fernando G,Axel D,Vito A,et al.3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016:Part1:Diagnosis and Medical Management[J].J Crohns Colitis,2017,11(1):3-25.
[13]Miehsler W,Puspok A,Oberhuber G,et al.Impact of Different Therapeutic Regimens on the Outcome of Patients with Crohn’s Disease of the Upper Gastrointestinal Tract[J].Inflamm Bowel Dis,2001,7(2):99-105.
[14]Hui-min Wu,Juan Wei,Kai Wang,et al.Mucus protectors:Promising therapeutic strategies for in inflammatory bowel disease[J].Med Hypotheses,2018(120):55-59.
[15]Johansson MEV,Gustafsson JK,Jessica Holmén-Larsson,et al.Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis[J].Gut,2013,63(2):281-291.
[16]Herrmann A,Davies J R,Lindell G,et al.Studies on the“insoluble”glycoprotein complex from human colon:identification of reduction-insensitive muc2 oligomers and c-terminal cleavage[J].J Biol Cheml,1999,274(22):15828-15836.
[17]Strugala V,Dettmar PW,Pearson JP.Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn's disease[J].Inte J Clin Prac,2008,62(5):762-769.
[18]Qin X.Damage of the Mucus Layer:The Possible Shared Critical Common Cause for Both Inflammatory Bowel Disease(IBD)and Irritable Bowel Syndrome(IBS)[J].Inflamm Bowel Dis,2017,23(2):E11-E12.
[19]Rhodes J M,Gallimore R,Elias E,et al.Faecal mucus degrading glycosidases in ulcerative colitis and Crohn's disease[J].Gut,1985,26(8):761-765.
[20]Dwarakanath AD,Campbell BJ,Tsai HH,et al.Faecal mucinase activity assessed in inflammatory bowel disease using 14C threonine labelled mucin substrate[J].Gut,1995,37(1):58-62.
[21]Piekkala,Maija,Hagstrom,et al.Low trypsinogen-1 expression in pediatric ulcerative colitis patients who undergo surgery[J].World J Gastroenterol,2013,19(21),3272-3280.
[22]He SH,Xie H.Modulation of histamine release from human colon mast cells by protease inhibitors[J].World J Gastroenterol,2004,10(3):337-341.
[23]隋丽,陈冬,张慧云,等.IL-29对胰蛋白酶诱导的肥大细胞PARs表达的调节作用[J].中国免疫学杂志,2014,30(5):609-612.
[24]Maeda S,Ohno K,Uchida K,et al.Intestinal protease-activated receptor-2 and fecal serine protease activity are increased in canine inflammatory bowel disease and may contribute to intestinal cytokine expression[J].J Vet Med Sci,2014,76(8):1119-1127.
[25]Nishise S,Sato T,Yu S,et al.Production of Interleukin-10 by Combining a Granulocyte and Monocyte Adsorption Carrier with Ulinastatin[J].Therapeutic Apheresis&Dialysis,2012,16(5):449-455.
[26]王荣国.奥曲肽对溃疡性结肠炎患者肠黏膜通透性的保护作用观察[J].中国医学工程,2015(11):92-92.
[27]钟英强,王连源,陈为宪.生长抑素治疗激素依赖型重度溃疡性结肠炎合并结肠大出血1例报告[J].新医学,2004,35(4):228.
[28]刘元山,陈剑群,朱炳喜.生长抑素对溃疡性结肠炎模型大鼠肠道炎性损伤的治疗作用[J].世界华人消化杂志,2009,17(17):1726-1731.
[29]Ruselervan Embden JG,Schouten WR,van Lieshout LM.Pouchitis:result of microbial imbalance?[J]Gut,1994,35(5):658-664.
[30]黄丽萍,袁文琴,陶学霞.奥曲肽对炎症性肠梗阻患者血浆CRP和IL-6浓度的影响及疗效观察[J].放射免疫学杂志,2013,26(5):662-663.
[2]Magro F,Gionchetti P,Eliakim R,et al.Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis.Part1:Definitions,Diagnosis,Extra-intestinal Manifestations,Pregnancy,Cancer Surveillance,Surgery,and Ileo-anal Pouch Disorders[J].JCrohns Colitis,2017(2):649-670.
[3]冯军鹏,陈秀,王瑞玲,等.不同胃液中胃蛋白酶含量的测定[J].中国医学工程,2012(3):3-5.
[4]Samloff IM,Stemmermann GN,Heilbrun LK,et al.Elevated serum pepsinogen I and II levels differ as risk factors for duodenal ulcer and gastric ulcer[J].Gastroenterology,1986,90(3):570-576.
[5]Gaw AJ,Williams LV,Spraggs CF,et al.Role of pepsin in the development of indomethacin-induced antral ulceration in the rat[J].Aliment Pharm Ther,1995,9(2):167-172.
[6]Huddy SP,Patel G,Heywood GC,et al.Prevention of acute gastric erosions in the rat by novel semi-synthetic amphipathic analogues of pepstatin[J].Gut,1988,29(11):1569-1577.
[7]Henriksson A,Khaled AKD,Conway PL.The Effect of Caecectomy on the Faecal Concentrations of Urobilinogen and Active Trypsin in Mice[J].Microb Ecol Heal Dis,1996,9(2):61-65.
[8]Zhou J,Jiang M,Yang X,et al.Unconjugated bilirubin ameliorates the inflammation and digestive protease increase in TNBS-induced colitis[J].Mol Med Rep,2017(2):1779-1784.
[9]Qin X.Etiology of inflammatory bowel disease:A unified hypothesis[J].World J Gastroenterol,2012,18(15):1708-1722.
[10]Senda S,Fujiyama Y,Bamba T,et al.Treatment of ulcerative colitis with camostat mesilate,a serine protease inhibitor[J].Int Med,1993,32(4):350-354.
[11]Sakuraba A,Iwao Y,Matsuoka K,et al.Endoscopic and Pathologic Changes of the Upper Gastrointestinal Tract in Crohn's Disease[J].Biomed Res Int,2014,Article ID610767.
[12]Fernando G,Axel D,Vito A,et al.3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016:Part1:Diagnosis and Medical Management[J].J Crohns Colitis,2017,11(1):3-25.
[13]Miehsler W,Puspok A,Oberhuber G,et al.Impact of Different Therapeutic Regimens on the Outcome of Patients with Crohn’s Disease of the Upper Gastrointestinal Tract[J].Inflamm Bowel Dis,2001,7(2):99-105.
[14]Hui-min Wu,Juan Wei,Kai Wang,et al.Mucus protectors:Promising therapeutic strategies for in inflammatory bowel disease[J].Med Hypotheses,2018(120):55-59.
[15]Johansson MEV,Gustafsson JK,Jessica Holmén-Larsson,et al.Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis[J].Gut,2013,63(2):281-291.
[16]Herrmann A,Davies J R,Lindell G,et al.Studies on the“insoluble”glycoprotein complex from human colon:identification of reduction-insensitive muc2 oligomers and c-terminal cleavage[J].J Biol Cheml,1999,274(22):15828-15836.
[17]Strugala V,Dettmar PW,Pearson JP.Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn's disease[J].Inte J Clin Prac,2008,62(5):762-769.
[18]Qin X.Damage of the Mucus Layer:The Possible Shared Critical Common Cause for Both Inflammatory Bowel Disease(IBD)and Irritable Bowel Syndrome(IBS)[J].Inflamm Bowel Dis,2017,23(2):E11-E12.
[19]Rhodes J M,Gallimore R,Elias E,et al.Faecal mucus degrading glycosidases in ulcerative colitis and Crohn's disease[J].Gut,1985,26(8):761-765.
[20]Dwarakanath AD,Campbell BJ,Tsai HH,et al.Faecal mucinase activity assessed in inflammatory bowel disease using 14C threonine labelled mucin substrate[J].Gut,1995,37(1):58-62.
[21]Piekkala,Maija,Hagstrom,et al.Low trypsinogen-1 expression in pediatric ulcerative colitis patients who undergo surgery[J].World J Gastroenterol,2013,19(21),3272-3280.
[22]He SH,Xie H.Modulation of histamine release from human colon mast cells by protease inhibitors[J].World J Gastroenterol,2004,10(3):337-341.
[23]隋丽,陈冬,张慧云,等.IL-29对胰蛋白酶诱导的肥大细胞PARs表达的调节作用[J].中国免疫学杂志,2014,30(5):609-612.
[24]Maeda S,Ohno K,Uchida K,et al.Intestinal protease-activated receptor-2 and fecal serine protease activity are increased in canine inflammatory bowel disease and may contribute to intestinal cytokine expression[J].J Vet Med Sci,2014,76(8):1119-1127.
[25]Nishise S,Sato T,Yu S,et al.Production of Interleukin-10 by Combining a Granulocyte and Monocyte Adsorption Carrier with Ulinastatin[J].Therapeutic Apheresis&Dialysis,2012,16(5):449-455.
[26]王荣国.奥曲肽对溃疡性结肠炎患者肠黏膜通透性的保护作用观察[J].中国医学工程,2015(11):92-92.
[27]钟英强,王连源,陈为宪.生长抑素治疗激素依赖型重度溃疡性结肠炎合并结肠大出血1例报告[J].新医学,2004,35(4):228.
[28]刘元山,陈剑群,朱炳喜.生长抑素对溃疡性结肠炎模型大鼠肠道炎性损伤的治疗作用[J].世界华人消化杂志,2009,17(17):1726-1731.
[29]Ruselervan Embden JG,Schouten WR,van Lieshout LM.Pouchitis:result of microbial imbalance?[J]Gut,1994,35(5):658-664.
[30]黄丽萍,袁文琴,陶学霞.奥曲肽对炎症性肠梗阻患者血浆CRP和IL-6浓度的影响及疗效观察[J].放射免疫学杂志,2013,26(5):662-663.
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