全国肠屏障功能障碍的基础与临床专题研讨会纪要

由《中华消化杂志》编辑委员会主办，上海交通大学附属第一人民医院承办的《全国肠屏障功能障碍的基础与临床》专题研讨会于2006年6月17日在上海召开。中华医学会和中华消化杂志有关领导出席了会议。与胃黏膜屏障功能相比，有关肠屏障功能障碍在消化界尚较生疏，因而本次会议引起国内同仁广泛兴趣，全国各地的专家共150人出席了本次研讨会。大会邀请了12名专家就有关肠屏障功能障碍的病因、发病机制、临床诊断、治疗等方面作了专题报告，在热烈的讨论基础上，初步制定了《肠屏障功能障碍临床诊治建议》。     

肠型脂肪酸结合蛋白在急性胰腺炎早期肠屏障损伤中的临床诊断价值

急性胰腺炎是一种特殊类型的急腹症,发病早期可导致肠屏障损伤。由于在肠屏障损伤早期缺少有效的诊断方法,患者往往因此而错失治疗的最佳时机,造成严重而复杂的并发症。肠型脂肪酸结合蛋白(I-FABP)是一种仅存在于胃肠道的胞浆蛋白,具有较好的器官特异性。研究发现血和尿I-FABP是诊断急性胰腺炎早期肠屏障损伤的良好指标。此文就急性胰腺炎致肠黏膜屏障功能障碍的发病机制以及I-FABP在急性胰腺炎早期肠屏障损伤中的诊断价值作一综述。     

肝衰竭与肠屏障功能障碍关系的研究进展

肝衰竭是指由多种因素引起的严重肝脏损害,导致肝脏本身合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,临床上出现以凝血机制障碍、黄疸、肝性脑病、腹水等为主要表现的一组症候群.肠屏障功能障碍引起肠源性内毒素血症在肝衰竭的发病中起着重要作用,是引起肝功能衰竭患者病情恶化和死亡的重要原因.因此,对肠屏障功能障碍的早期诊断并采取有效的防治措施显得极其重要.但是,由于肠道功能的复杂性及缺乏明确的功能监测指标,对于肠屏障功能障碍的发生机制、诊治等问题尚缺乏一致意见.现将目前关于肝衰竭与肠屏障功能障碍之间关系的研究进展综述如下.     

重症急性胰腺炎肠屏障功能障碍研究

重症急性胰腺炎患者常伴有肠屏障功能障碍,正常肠道屏障由机械屏障、化学屏障、免疫屏障与微生物屏障4部分构成.肠屏障功能障碍通常指上述4种屏障功能出现不同程度的破坏,本文就重症急性胰腺炎肠道屏障功能障碍时上述4种屏障的病理生理改变作一概述.     

重症急性胰腺炎对肠黏膜屏障损伤影响的研究进展

肠黏膜屏障功能是肠道的重要特征之一,大量研究表明重症急性胰腺炎(SAP)患者易发生肠屏障功能障碍,而肠屏障功能障碍又可进一步继发感染,甚至诱发和加重全身炎症反应综合征(SIRS)、多器官功能障碍综合征(MODS)。本文就SAP对肠黏膜屏障损伤影响的研究进展作一简要综述。     

《肠屏障功能障碍的基础与临床》专题研讨会征文通知

南《中华消化杂志》编辑委员会主办,上海交通大学附属第一人民医院承办的《肠屏障功能障碍的基础与临床》专题研讨会定于2006年6月17日—18日在上海召开。会议期间,将邀请此领域的著名专家对肠屏障功能障碍的发病机制、与各疾病间的关系及其防治等方面展开讨论。现征集相关基础和临床研究论文,内容包括:肠屏障功能障碍的病因、病理生理机制、临床监测和评估、预防和治疗等。请将论文全文(按中华消化杂志约稿要求)和800字摘要各一份邮寄至:上海市北京西路1623     

急性胰腺炎肠道功能障碍的发病机制与治疗

急性胰腺炎可导致肠道功能障碍, 包括肠道屏障损伤和肠道动力障碍, 此时肠道中滋生大量致病菌, 他们可通过破损的肠黏膜易位至其他器官, 加重胰腺炎病情, 并可引起多器官功能障碍. 本文综述了近年来急性胰腺炎肠功能障碍的发病机制和治疗进展.     

梗阻性黄疸对肠黏膜屏障的影响

肠黏膜屏障包括机械屏障、免疫屏障、生物屏障和化学屏障,四者共同维持肠黏膜的正常防御功能。梗阻性黄疸患者引起肠黏膜屏障损伤,导致细菌移位及内毒素血症,后者又加重屏障功能障碍。本文主要就梗阻性黄疸对肠黏膜屏障损伤的机制作一综述。     

炎症性肠病肠黏膜屏障功能障碍研究及治疗进展

近年来对肠道功能的认识已经从最初的营养物质的消化吸收发展到对屏障功能的关注。肠黏膜屏障在防御外来抗原物质对机体的侵袭,保持机体内环境相对稳定,维持机体的正常生命活动等方面有重要的作用。炎症性肠病（IBD）的发病机制尚未完全明确,主要与遗传、环境、自身免疫、感染等有关。研究表明,IBD患者都存在不同程度的肠黏膜屏障功能障碍。本文就此作一综述。     

肠屏障功能障碍临床诊治建议

一、概念 肠屏障功能障碍（intestinal barrier dysfunction）是各种原因引起的肠黏膜损伤、萎缩，肠通透性增加，肠菌群失调，从而导致细菌和（或）内毒素易位，并可诱发和（或）加重全身炎症反应和多器官功能障碍。肠屏障功能障碍对危重疾病的发生、发展、转归有重要影响。肠屏障功能障碍在危重病患者中较常见，但目前尚缺乏较为客观的临床诊断标准与统一的治疗方案。     

肠屏障功能检测方法的研究现状及展望

肠屏障功能障碍是导致全身炎症反应综合征、多器官功能不全综合征,甚至多器官功能衰竭的一个重要因素。早期判断患者有无肠黏膜损伤并进行有效干预意义重大,因此加大对肠屏障功能检测方法的研究力度具有重要意义。本文就肠脂肪酸结合蛋白、瓜氨酸、D-乳酸等常用的肠屏障功能检测指标及方法予以综述。     

Confirmation and prevention of intestinal barrier dysfunction and bacterial translocation caused by methotrexate

When intestinal barrier function is damaged bacterial translocation (BT) can occur. The injury to intestinal barrier function caused by chemotherapy has been investigated in some studies, however, definitive evidence of BT caused by chemotherapy is lacking. The aim of this study was to investigate small intestinal barrier dysfunction and BT and to evaluate the preventive effect of granulocyte colony-stimulating factor (G-CSF) on intestinal barrier dysfunction and BT in a rat model of chemotherapy. Sprague-Dawley rats were treated with methotrexate (MTX; 3.5 mg/kg) for 3 days to induce intestinal barrier dysfunction and BT, gavaged Escherichia coli TG1 labeled with green fluorescent protein for 2 days to track BT, and G-CSF (10 μg/kg) for 4 days to prevent intestinal barrier dysfunction and BT. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following administration by gavage. Representative tissue specimens from the mesenteric lymph nodes, spleen, liver, and kidney were aseptically harvested for bacteria culture in ampicillin-supplemented medium. Light microscopy was performed on intestinal samples. MTX induced significant mucosal and villous atrophy in ileum and significantly increased intestinal permeability. MTX also induced noticeable BT. G-CSF significantly increased the mucosal thickness and villous height of the ileum and decreased intestinal permeability and BT. In conclusion, MTX caused intestinal barrier dysfunction and BT, and G-CSF prevented intestinal barrier dysfunction and BT.     

肺部疾病对肠黏膜屏障影响的研究进展

近年来,肺部常见疾病多伴随胃肠功能障碍,严重影响患者预后,探索肺部疾病与肠黏膜屏障的关系逐渐受到重视。本文现就肠黏膜屏障的组成（包括机械屏障、生物屏障、免疫屏障、化学屏障）以及肺部疾病（肺炎、哮喘、慢性阻塞性肺疾病、特发性肺纤维化）对肠黏膜功能影响的作用机制进行综述,旨在为临床早发现、早治疗胃肠功能障碍提供理论依据。     

肥大细胞在重症急性胰腺炎肠黏膜屏障功能损伤中的作用

肥大细胞(MC)是神经-免疫-内分泌系统中的关键细胞,参与调节机体多种病理生理过程。重症急性胰腺炎(SAP)发生时,大量MC被激活,释放多种细胞因子以及炎性介质,与SAP并发肠黏膜屏障功能损伤密切相关。本文就MC在SAP肠黏膜屏障功能损伤中的作用作一综述。     

肠道菌群与脓毒症相互关系的研究进展

脓毒症的发生发展与肠道菌群失调密切相关.肠道菌群失调可以通过肠黏膜屏障功能破坏、黏膜免疫功能破坏和细菌移位等环节诱导脓毒症的发生.同时脓毒症也可以加重肠道菌群失调,加重肠黏膜屏障功能破坏,导致机体多器官功能障碍.本文通过探讨肠道菌群和脓毒症之间的相互关系,为脓毒症临床干预提供思路.     

Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome

The etiopathogenesis of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, is not well known. The most accepted hypothesis is that IBS is the result of the disturbance of the 'brain-gut axis.' Although the pathophysiological mechanisms of intestinal dysfunction are complex and not completely understood, stress, infections, gut flora, and altered immune response are thought to play a role in IBS development. The intestinal barrier, composed of a single-cell layer, forms a physical barrier that separates the intestinal lumen from the internal milieu. The loss of integrity of this barrier is related with mucosal immune activation and intestinal dysfunction in IBS. The number of mast cells and T lymphocytes is increased in the intestinal mucosa of certain IBS patients, and the mediators released by these cells could compromise the epithelial barrier function and alter nerve signaling within the enteric nervous system. The association of clinical symptoms to structural and functional abnormalities of the mucosal barrier in IBS patients highlights the importance of understanding the physiological role of the gut barrier in the pathogenesis of this disorder. This review summarizes the clinical and experimental evidences indicating the cellular and molecular mechanisms of IBS symptomatology, and its relevance for future translational research.     

Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut microbiota. An important next step is to elucidate a human-relevant “map’’ of microbiota-host interactions that regulate the metabolic health of the host. An improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat obesity. Intestinal mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions, including cancer, neurodegeneration, and aging. The mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly understood. Understanding the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier breakage. Changes in the composition and function of the gut microbiota, i.e., dysbiosis, are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier dysfunction. Many effects of the microbiota on the host are mediated by microbiota-derived metabolites. In this review, we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic diseases. The design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.     

P2X7 receptor as the regulator of T-cell function in intestinal barrier disruption

The intestinal mucosa is a highly compartmentalized structure that forms a direct barrier between the host intestine and the environment, and its dysfunction could result in a serious disease. As T cells, which are important components of the mucosal immune system, interact with gut microbiota and maintain intestinal homeostasis, they may be involved in the process of intestinal barrier dysfunction. P2X7 receptor (P2X7R), a member of the P2X receptors family, mediates the effects of extracellular adenosine triphosphate and is expressed by most innate or adaptive immune cells, including T cells. Current evidence has demonstrated that P2X7R is involved in inflammation and mediates the survival and differentiation of T lymphocytes, indicating its potential role in the regulation of T cell function. In this review, we summarize the available research about the regulatory role and mechanism of P2X7R on the intestinal mucosa-derived T cells in the setting of intestinal barrier dysfunction.     

Commensal-innate immune miscommunication in IBD pathogenesis

Commensal microbiota plays a key role in the health and disease of the host. The innate immune system comprises an essential functional component of the intestinal mucosal barrier, maintaining hyporesponsiveness to omnipresent harmless commensals in the lumen, but rapidly recognizing and combating invading bacteria through diverse antimicrobial mechanisms. Interactions between commensals and innate immune cells are constant, multidimensional and entirely context-dependent. Environment, genetics and host defense differentially modulate commensal-innate immune effects and functions in the intestinal mucosa. In IBD, dysbiosis, mucus layer disruption, impairment in bacterial clearance, intestinal epithelial cell barrier dysfunction and/or immune cell deregulation may lead to commensal-innate immune miscommunication, which critically drives mucosal inflammation and associated cancer.