肠屏障功能损伤机制及其临床检测方法研究现状

doi:10.16689/j.cnki.cn11-9349/r.2020.04.006

摘要
图/表
参考文献
相关文章 (0)

全文: PDF (1111 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要肠道作为机体的消化器官，除了具有消化吸收和蠕动功能外，还具有内分泌、免疫调节和黏膜屏障功能。生理状态下的肠屏障功能可消化和吸收营养物质、有效防止机体内环境受到有害物质的侵害，保障机体内环境稳定，由机械屏障、免疫屏障、化学屏障和生物屏障共同组成。肠屏障功能损伤机制复杂，临床上多种因素可直接或间接破坏肠屏障功能，这些因素包括严重感染、创伤、烧伤、肠梗阻、急性胰腺炎、重度营养不良、重度失血、失液、长期应用广谱抗生素或免疫抑制剂、电离辐射、放疗、化疗等。这些因素可从一个或多个方面造成肠屏障功能损伤，导致肠内病原微生物及其代谢物经门静脉和淋巴系统纵向易位入血，引发菌血症和毒血症，严重时可导致全身炎症反应综合征和多系统器官功能衰竭。目前检测多采用血液中D-乳酸的水平、二胺氧化酶、内毒素等来评估肠屏障功能。临床工作中应予重视肠屏障功能障碍的治疗。本文对肠道屏障及其损伤发生的机制，诊断和治疗方法进行综述。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	尉浩斌
	张小丹
	李苏宜

关键词 ：肠屏障功能, 二胺氧化酶, 内毒素, D-乳酸

Abstract：As the digestive organ of the body, the intestinal tract not only has the functions of digestion, absorption and peristalsis, but also has the functions of endocrine, immune regulation and mucosal barrier. The intestinal barrier function under physiological conditions can digest and absorb nutrients, effectively prevent the internal environment from being harmed by harmful substances, ensure the stability of internal environment, it consists of mechanical barrier, immune barrier, chemical barrier and biological barrier. The mechanism of intestinal barrier function damage is complex, and a variety of clinical factors can directly or indirectly damage intestinal barrier function, including severe infection, trauma, burn, intestinal obstruction, acute pancreatitis, severe malnutrition, severe blood loss, fluid loss, long-term application of broad-spectrum antibiotics or immunosuppressive agents, ionizing radiation, radiotherapy, chemotherapy, etc. These factors can lead to impaired intestinal barrier function in one or more ways, causing vertical translocation of intestinal pathogenic microorganisms and their metabolites into the blood through the portal vein and lymphatic system, causing bacteremia and toxaemia, and in severe cases, leading to systemic inflammatory response syndrome and multi-system organ failure. At present, the level of D-lactic acid, diamine oxidase and endotoxin in blood are mostly used to evaluate the intestinal barrier function. Attention should be paid to the treatment of intestinal barrier dysfunction in clinical work. In this paper, the mechanism, diagnosis and treatment of intestinal barrier and its injury are reviewed.

Key words： Intestinal barrier function Diamine oxidase Endotoxin D-lactic acid

通讯作者: 李苏宜，电子邮箱：njlisuyi@sina.com

引用本文:

尉浩斌，张小丹，李苏宜. 肠屏障功能损伤机制及其临床检测方法研究现状[J]. 肿瘤代谢与营养电子杂志, 2020, 7(4): 407-414.
Yu Haobin,Zhang Xiaodan, Li Suyi. Research status of the mechanism of intestinal barrier function injury and its clinical detection methods. Electron J Metab Nutr Cancer, 2020, 7(4): 407-414.

1.KNIG J, WELLS J, CANI P D, et al. Human intestinal barrier function in health and disease［J］. Clin Transl Gastroenterol, 2016, 7(10): e196.
2.SHI N, LI N, DUAN X, et al. Interaction between the gut microbiome and mucosal immune system［J］. Mil Med Res, 2017, 4: 14.
3.HUANG X Z, ZHU L B, LI Z R, et al. Bacterial colonization and intestinal mucosal barrier development［J］. World J Clin Pediatr, 2013, 2(4): 46-53.
4.MAJKA G, WIECEK G, RTTEK M, et al. The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation［J］. Biometals, 2016, 29(6): 1019-1033.
5.ASSIMAKOPOULOS S F, SCOPA C D, CHARONIS A, et al. Experimental obstructive jaundice disrupts intestinal mucosal barrier by altering occludin expression: beneficial effect of bombesin and neurotensin［J］. J Am Coll Surg, 2004, 198(5): 748-757.
6.李旌, 黄煌, 梅璐, 等. 酪酸梭菌对食物过敏小鼠肠道屏障功能的影响［J］. 重庆医学, 2017, 46(22): 3028-3032.
7.王慧, 毛晶磊, 吴艳敏, 等. 真人养脏汤对溃疡性结肠炎大鼠肠道黏膜屏障功能的保护作用［J］. 中国病理生理杂志, 2017, 33(11): 2053-2059.
8.REN T, WANG Q, XU Y, et al. Enhanced oral absorption and anticancer efficacy of cabazitaxel by overcoming intestinal mucus and epithelium barriers using surface polyethylene oxide (PEO) decorated positively charged polymer-lipid hybrid nanoparticles［J］. J Control Release, 2018, 10: 423-438.
9.郑丽萍, 文武. 双歧杆菌与复方谷氨酰胺肠溶胶囊联合用药对胃肠功能紊乱患者肠黏膜屏障功能以及炎症因子的影响［J］. 四川生理科学杂志, 2018, 40(2): 102-105.
10.周文浩, 蒋晓忠, 王昌松, 等. 乙型肝炎肝硬化患者血清IGF.I水平与肠道屏障功能损害的关系分析［J］. 实用肝脏病杂志, 2018, 2l(4): 101-104.
11.RESCIGNO M. The intestinal epithelial barrier in the control of homeostasis and immunity［J］. Trends Immunol, 2011, 32(6): 256-264.
12.KONJAR , FERREIRA C, BLANKENHAUS B, et al. Intestinal Barrier Interactions with Specialized CD8 T Cells［J］. Front Immunol, 2017, 8(8): 1-15.
13.HUGGINS M A, JOHNSON H L, JIN F, et al. Perforin expression by CD8 T cells is sufficient to cause fatal brain edema during experimental cerebral malaria［J］. Infect Immun, 2017, 85(5): e00985-00916.
14.OSHIMA T, MIWA H. Gastrointestinal mucosal barrier function and diseases［J］. J Gastroenterol, 2016, 51(8): 768-778.
15.YANO H, KATO Y, MATSUDA T. Acute exercise induces gastrointestinal leakage of allergen in lysozyme-sensitized mice［J］.Eur J Appl Physiol, 2002, 87(4-5): 358-364.
16.KOLTES D A, LESTER H D, FROST M, et al. Effects of bacitracin methylene disalicylate and diet change on gastrointestinal integrity and endotoxin permeability in the duodenum of broiler chicken［J］. BMC Res Notes, 2017, 10(1): 470-478.
17.SERINO M, LUCHE E, CHABO C, et al. Intestinal microflora and metabolic diseases［J］. Diabetes Metab, 2009, 35(4): 262-272.
18.王强, 薛东波. 肠道菌群通过影响胆汁酸代谢参与胆囊胆固醇结石形成［J］. 肝胆胰外科杂志, 2020, 32(1): 6-8, 25.
19.EFCKOV Z, BUJNKOV D. Effect of pre- and post-weaning high-fat dietary manipulation on intestinal microflora and alkaline phosphatase activity in male rats［J］. Physiol Res, 2017, 66(4): 677-685.
20.UR R S, KHAN S, CHAND N, et al. In vivo effects of Allium cepa L. on the selected gut microflora and intestinal histomorphology in broiler［J］. Acta Histochem, 2017, 119(5): 446-450.
21.LU K, MAHBUB R, FOX J G. Xenobiotics: Interaction with the intestinal microflora［J］. ILAR J, 2015, 56(2): 218-227.
22.JOHN J, ROEDIGER K, SCHROEDL W, et al. Development of intestinal microflora and occurrence of diarrhoea in sucking foals: effects of Bacillus cereus var. toyoi supplementation［J］. BMC Vet Res, 2015, 11(1): 34-45.
23.YUAN Z H, WANG J P, ZHANG K Y, et al. Effect of vanadium and tea polyphenols on intestinal morphology, microflora and short-chain fatty acid profile of laying hens［J］. Biol Trace Elem Res, 2016, 174(2): 419-427.
24.SCHUMANN A, NUTTEN S, DONNICOLA D, et al. Neonatal antibiotic treatment alters gastrointestinal tract developmental gene expression and intestinal barrier transcriptome［J］. Physiol Genomics, 2005, 23(2): 235-245.
25.VAN AMPTING M T, SCHONEWILLE A J, VINK C, et al. Damage to the intestinal epithelial barrier by antibiotic pretreatment of salmonella-infected rats is lessened by dietary calcium or tannic acid［J］. J Nutr, 2010, 140(12): 2167-2172.
26.SALEEM B, OKOGBULE-WONODI A C, FASANO A, et al. Intestinal barrier maturation in very low birthweight infants: relationship to feeding and antibiotic exposure［J］. J Pediatr, 2017, 183: 31-36.
27.PALLASCH T J. Antibiotic resistance［J］. Dent Clin North Am, 2003, 47(4): 623-639.
28.VERA-LISE T M, GERD C E, VERA C, et al. Antibiotic treatment affects intestinal permeability and gut microbial composition in wistar rats dependent on antibiotic class［J］. PLoS One, 2015, 10(12): e0144854.
29.GASCHE Y, COPIN J C, SUGAWARA T, et al. Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia［J］. J Cereb Blood Flow Metab, 2016, 21(12): 1393-1400.
30.LI Y, SONG Z, KERR K A, et al. Chronic social stress in pigs impairs intestinal barrier and nutrient transporter function, and alters neuro-immune mediator and receptor expression［J］. PLoS One, 2017, 12(2): e0171617.
31.CHEN W Y, WANG M, ZHANG J, et al. Acrolein disrupts tight junction proteins and causes ER stress-mediated epithelial cell death leading to intestinal barrier dysfunction and permeability［J］. Am J Pathol, 2017, 187(12): 2686-2697.
32.ZHENG G, FON GV, MEIXNER W, et al. Chronic stress and intestinal barrier dysfunction: Glucocorticoid receptor and transcription repressor HES1 regulate tight junction protein Claudin-1 promoter［J］. Sci Rep, 2017, 7(1): 4502-4519.
33.DENG W, ABLIZ A, XU S, et al. Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin［J］. Mol Med Rep, 2016, 14(4): 3525-3534.
34.BRGEON J, CORON E, DA S A, et al. Sacral nerve stimulation enhances early intestinal mucosal repair following mucosal injury in a pig model［J］. J Physiol, 2016, 594(15): 4309-4318.
35.马怀幸, 李苏宜. 肿瘤营养不良的内科治疗原理和原则［J］. 肿瘤学杂志, 2018, 24(9): 849-855.
36.HERNNDEZ-MORENO A, VIDAL-CASARIEGO A, CALLEJA-FERNNDEZ A, et al. Chronic enteritis in patients undergoing pelvic radiotherapy: prevalence, risk factors and associated complications［J］. Nutr Hosp, 2015, 32(5): 2178-2183.
37.杨洋, 赵勇. 丙氨酰谷氨酰胺及双歧杆菌三联活菌胶囊在结直肠癌术后辅助化疗中对肠道屏障功能的影响［J］. 中国现代医学杂志, 2020, 30(15): 79-84.
38.NEJDFORS P, EKELUND M, JEPPSSON B, et al. Mucosal in vitro permeability in the intestinal tract of the pig, the rat, and man: species- and region-related differences［J］. Scand J Gastroenterol, 2017, 35(5): 501-511.
39.LIU Y C, QI Z W, GUO S G, et al. Role of corticotrophin-releasing hormone in the cerebral infarction-related gastrointestinal barrier dysfunction［J］. World J Emerg Med, 2011, 2(1): 59-65.
40.高帆, 许青文, 徐鹏远, 等. D-乳酸、i-FABP作为肠屏障功能障碍预警指标的生物学意义［J/CD］. 临床医药文献电子杂志, 2019, 6(5): 22.
41.NEVADO R, FORCN R, LAYUNTA E, et al. Neomycin and bacitracin reduce the intestinal permeability in mice and increase the expression of some tight-junction proteins［J］. Rev Esp Enferm Dig, 2015, 107(11): 672-676.
42.任小龙, 丁连安, 曲林林. 他克莫司对小鼠肠黏膜结构的影响［J］. 肠外与肠内营养, 2014, 21(3): 172-174, 178.
43.王裴, 冯燕海, 王顺宾, 等. 肠型脂肪酸结合蛋白在严重烧伤小鼠早期肠屏障功能损害评估中的意义［J］. 中华烧伤杂志, 2019, 35(6): 459-463.
44.郝娜, 杨洪涛. CKD4期患者营养状态与肠道黏膜免疫屏障的关系及中药结肠透析干预的疗效［J］. 世界华人消化杂志, 2017, 25(10): 940-945.
45.周开国, 付研. 胃肠道屏障功能障碍的研究进展［J］. 中华普通外科杂志, 2012, 27(6): 514-517.
46.ZHONG W, LI Q, ZHANG W, et al. Modulation of intestinal barrier and bacterial endotoxin production contributes to the beneficial effect of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation in rats［J］. Biomolecules, 2015, 5(4): 2643-2658.
47.刘志慧, 于泳浩, 李佩铂, 等. 帕瑞昔布钠对脓毒症大鼠肠黏膜屏障功能的影响［J］. 国际麻醉学与复苏杂志, 2018, 39(5): 395-399.
48.席进, 葛思堂, 左芦根, 等. 绿茶多酚抑制肠道JAK2/STAT3信号通路保护三硝基苯磺酸诱导的小鼠结肠炎肠黏膜屏障［J］. 细胞与分子免疫学杂志, 2018, 34(3): 237-241.
49.王南瑶, 李苏宜. 肿瘤患者肠功能不全及其治疗［J］. 肿瘤学杂志, 2014, 20(8): 635-638.
50.REINTAM BLASER A, MALBRAIN M L, STARKOPF J, et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems［J］. Intensive Care Med, 2012, 38: 384-394.
51.VAN ZANTEN ARH. How to improve worldwide early enteral nutrition performance in intensive care units［J］. Crit Care, 2018, 22(1): 315.
52.USUI M, HAYASAKI A, FUJII T, et al. Early enteral feeding of daikenchuto stimulates early bowel movement with increased portal venous blood flow after living donor liver transplantation［J］. Transplant Proc, 2018, 50(9): 2690-2694.
53.吴国豪.肠屏障功能障碍及防治对策［J］. 肠外与肠内营养, 2004, 11(5): 313-316.
54.杜小东, 罗利飞.溃疡性结肠炎患者肠道菌群和肠黏膜屏障的变化及益生菌的干预作用［J］. 中国微生态学志, 2019, 31(2): 193-196.
55.陈曦, 夏兴洲, 孙霞, 等．双歧杆菌三联活菌联合美沙拉嗪治疗溃疡性结肠炎效果分析［J］. 中华全科医师杂志, 2014, 13(3): 223-225.
56.王忠亮, 王坚强. 双歧三联活菌胶囊对溃疡性结肠炎患者血清白介素-10和肿瘤坏死因子-α水平的影响及疗效观察［J］. 中国微生态学杂志, 2014, 26(8): 914-916.