MCs介导的COX2-PGE2-Eps信号通路在IBS内脏高敏感性中的机制研究

肠易激综合征(irritable bowel syndrome,IBS)是功能性胃肠病的一种,其病理生理机制复杂,涉及遗传因素、心理社会因素、黏膜低度炎症、肠道屏障改变、肠道菌群紊乱、神经免疫异常及内脏高敏感性等多种机制.近年来,内脏高敏感性在IBS中的作用机制成为研究热点.肥大细胞(mast cells,MCs)是分...     

肥大细胞活化参与肠易激综合征发病的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是临床常见的功能性肠病,发病机制复杂,现有的治疗药物难以取得满意的效果.IBS可能与脑-肠功能失调、内脏高敏感、胃肠动力异常、肠道菌群紊乱、肠道通透性增高等因素有关.近年来,肠黏膜免疫紊乱在IBS中的作用受到重视.肥大细胞(mast cell,MCs)是广泛分布于胃肠道的免疫细胞,多种原因引起的MCs活化脱颗粒,通过MCs释放的活性介质作用于邻近的上皮细胞,神经元细胞,平滑肌细胞或其他免疫细胞,常可导致IBS内脏高敏感、肠道动力异常、上皮通透性增高、肠道持续低度炎症的发生.许多研究已经证实MCs在IBS的病理生理过程中发挥着关键作用.因此,本文就近年来MCs活化参与IBS的相关机制进行综述,以期为进一步研究IBS的发病机制以及治疗药物的研发提供依据.     

基于肥大细胞论肠易激综合征的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是常见的功能性胃肠疾病,其发病率、复发率高,严重影响患者的生活质量,对社会医疗资源和家庭经济造成极大负担.多数学者认为压力、感染、食物过敏等可通过神经-免疫-内分泌系统介导IBS的发生,并一直将其作为功能性疾病加以研究.腹痛为IBS典型表现,与内脏高敏密切相关.近些年随着IBS"低度炎症状态"的提出,IBS发生的相关免疫机制成为研究热点.肥大细胞(mast cell,MC)为肠道重要的免疫细胞,其数目的改变,活化脱颗粒效应以及与感觉神经的相互作用在IBS的发生中起着重要作用.本文将主要就MC与IBS发病的关系作一综述.     

肥大细胞与腹泻型肠易激综合征的关系

肠易激综合征(IBS)是一组以腹痛或腹部不适同时伴排便习惯及大便性状改变为主要症状的肠道功能性疾病,包括腹泻型(IBS-D)、便秘型(IBS-C)和腹泻便秘交替型(IBS-A), 其症状无特异性并与一些肠道器质性病变的症状多有重叠,诊断主要建立在症状学积分和排除器质性病变的基础上,因此临床治疗比较困难.IBS的发病机制尚不清楚,但近年随着IBS神经-免疫-内分泌网络调控机制的提出,越来越多的研究表明肥大细胞(MC)在发病机制中起了重要的作用.了解MC与IBS-D的相关性,将可能为IBS-D的临床治疗提供新思路.     

神经生长因子与肥大细胞在肠易激综合征模型大鼠肠道的研究

神经生长因子（NGF）是一种影响神经系统生长发育的生物活性物质，是外周感觉神经和交感神经系统分化与生存所必需的一种蛋白质。NGF还是炎症致痛的重要中介物质，并与躯体及内脏痛觉过敏有关。既往的研究已知，NGF可由肥大细胞（MC）合成和释放。近年来对肠易激综合征（IBS）的研究发现，IBS患者存在肠道敏感性改变及MC数量增多，但NGF在肠道的表达及是否参与IBS的发病机制尚不清楚。     

肥大细胞在肠易激综合征发病机制中的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是以腹痛、腹部不适伴排便习惯改变和/或大便性状异常为特征的常见功能性胃肠病.IBS全球患病率为2%-15%.本病病因及发病机制尚不十分明确,目前认为多与胃肠动力异常、内脏高敏、感染与炎症、神经-内分泌失调、精神心理、食物过敏等多种因素有关.近年来提出的"神经-免疫-内分泌网络"理论在IBS发病机制中占有重要地位.研究发现,胃肠道的肥大细胞(mast cells,MCs)在IBS的发病中发挥着重要作用.本文拟以MCs在IBS中的发病机制的最新研究进展作一综述.     

肥大细胞异型性在肠易激综合征发病机制中的作用研究

目的　探讨肥大细胞在肠易激综合征 (IBS)患者肠道内分布、变化及其临床意义 ,并对其异型性在IBS发病机制中的作用进行相关研究。方法　经结肠镜钳取 2 4名正常人和 5 9例肠易激综合征患者回肠末端、盲肠和降结肠黏膜 ,分别采用抗人肥大细胞类胰酶抗体标识肥大细胞 ,并应用免疫组化方法检测了肥大细胞数目、活性变化和其雌激素受体表达的差异。结果　 1 IBS患者回肠末端和盲肠黏膜肥大细胞数目增多、活性增强 ,降结肠黏膜肥大细胞数目与正常组无显著差别 ,但腹泻型IBS患者降结肠肥大细胞活性增强 (P <0 .0 1)。 2 肥大细胞与雌激素受体阳性 (ER + )细胞显著相关 (R =0 .884,P <0 .0 1) ,但每例肥大细胞和ER +细胞的积分不同。结论　回肠末端和盲肠肥大细胞活性增强提示此处可能为IBS发病的关键部位 ;肥大细胞异型性与IBS病理生理过程密切相关     

感染后肠易激综合征肠道局部免疫-神经-内分泌网络功能的变化

肠易激综合征(IBS)是临床上最常见的功能性胃肠病之一。近年来肠道炎症,特别是急性肠道感染后遗留的肠道黏膜低度炎症在IBS中的作用越来越受到重视,此文就肠道黏膜低度炎症和肠道局部免疫变化、肠道神经-内分泌网络变化在IBS发病中的作用作一综述。     

应激与肠易激综合征相关性研究

肠易激综合征(irritable bowel syndrome,IBS)是一种以脑-肠互动异常为核心的功能性肠病,在我国和世界范围内发病率高,严重影响患者生活质量。IBS与应激密切相关,患者多合并急慢性应激状态与精神障碍共病。应激通过塑造内脏高敏感性、促进肠道低度炎症和干扰肠道菌群等机制参与IBS的发生与发展。本文就应激在IBS发病中的作用及相关临床干预方法作一概述,为IBS的预防、治疗和后续研究提供理论依据。     

腹泻为主的IBS患者空肠肥大细胞功能存在数量异常

过去曾有报道，远端肠道肥大细胞的数量增加和功能增强与肠易激综合征（IBS）的发生发展及严重程度关系密切，但肥大细胞在小肠内的情况尚无定论。近期Gut上的一篇文章报道了小肠肥大细胞活性和IBS关系的文章。该研究通过Watson胶囊内镜获取20例以腹泻为主的IBS（D-IBS）患者的空肠黏膜活组织标本及肠液，同时采集患者血液标本，对照组为14例健康志愿者。在相同的心理应激（Holmes-Rahe标准）和抑郁（Beck标准）情况下，比较D—IBS患者和健康对照组间的不同，并用组织标本HE染色，镜下计数淋巴细胞以评价炎症反应程度，以CD117（c-kit）为标记物，     

Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome

The pathogenesis of irritable bowel syndrome (IBS) is considered to be multifactorial and includes psychosocial factors, visceral hypersensitivity, infection, microbiota and immune activation. It is becoming increasingly clear that low-grade inflammation is present in IBS patients and a number of biomarkers have emerged. This review describes the evidence for low-grade inflammation in IBS and explores its mechanism with particular focus on gastrointestinal motor dysfunction. Understanding of the immunological basis of the altered gastrointestinal motor function in IBS may lead to new therapeutic strategies for IBS.     

Intestinal infection and irritable bowel syndrome

The observation that the symptoms of irritable bowel syndrome (IBS) in some patients might follow an episode of acute gastroenteritis came from epidemiological studies. Both retrospective and prospective studies suggest that between 4% and 26% of patients develop IBS for the first time after gastroenteritis. The diagnosis of post-infectious IBS is typically made from the history. In addition, as with the diagnosis of IBS more generally, it is important to exclude other clinical causes for persistent bowel dysfunction. There is little, if any, evidence to support the widely-held view that patients with post-infectious IBS carry a better prognosis than IBS patients more generally. The management of patients with post-infectious IBS is the standard approach that might be applied to all patients with IBS. Post-infectious IBS patients may differ from IBS patients in general in having a low-level of intestinal inflammation. Work in animal models, and detection of low-grade inflammation in intestinal biopsies combined with markers of intestinal inflammation such as faecal calprotectin all indicate a strong possibility that persisting inflammation after the acute infection may be important in the pathogenesis of post-infectious IBS.     

Irritable bowel syndrome: Diagnosis and pathogenesis

Irritable bowel syndrome (IBS) is a common gastro-intestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome Ⅲ criteria. A combination of the Rome Ⅲ criteria, a physical examination, blood tests, gastros-copy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS:heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following:genetic factors, dietary intake, intestinal flora, or lowgrade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI-and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut.     

Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome

Serotonin(5-HT) and the serotonin transporter(SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome(IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mR NA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microR NAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.     

A role for inflammation in irritable bowel syndrome?

Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.     

Is Irritable Bowel Syndrome a Low-Grade Inflammatory Bowel Disease?

Irritable Bowel Syndrome (IBS) is multifactorial in its etiology and heterogeneous in its clinical presentation and pathogenesis. It is recognized that inflammation plays an important role in symptom generation, at least in a subset of patients with IBS. Previous gastroenteritis has been identified as the most important risk factor for IBS, and several studies reported that a substantial proportion of patients with gastrointestinal infection develops IBS symptoms,which can persist for several years. Recent studies have demonstrated that a proportion of IBS patients without any history of enteritis has signs of immune activation in the gut. There is clinical overlap between IBS and inflammatory bowel disease (IBD), with IBS-like symptoms frequently reported in patients before the diagnosis of IBD, and a higher than expected percentage reports of IBS symptoms in patients in remission from established IBD. Thus,these conditions may coexist with a higher than expected frequency, or may exist on a continuum, with IBS and IBD at different ends of the same spectrum. This article examines these relation-ships using immune activation and inflammation as a common pathogenic process to IBD and a subset of IBS patients.     

What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some recent reports have found an interesting correlation between obesity and IBS.A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD,leading to an increased cardiovascular risk,and IBS,leading to microbial dysbiosis,impaired intestinal barrier and altered intestinal motility.It is not known when considering local and systemic inflammation/immune system activation,which one has greater importance in NAFLD and IBS pathogenesis.Also,the nervous system is implicated.In fact,inflammation participates in the development of mood disorders,such as anxiety and depression,characteristics of obesity and consequently of NAFLD and,on the other hand,in intestinal hypersensitivity and dysmotility.     

Putative inflammatory and immunological mechanisms in functional bowel disorders.

The observations that irritable bowel syndrome (IBS) may be precipitated by an acute enteric infection, or occurs commonly in patients in remission from inflammatory bowel disease (IBD) has prompted consideration of inflammation as a putative basis for symptom generation in IBS. In this regard, IBS may follow a pattern of pathogenesis that is similar to asthma--which was once considered a psychosomatic disease. This review examines the basic scientific evidence of a functional interface between the immune and sensory-motor systems of the gut and discusses how this may be relevant to a subgroup of IBS patients. In addition, review will examine the implications of this for the diagnosis and treatment of IBS.     

Unraveling the ties between irritable bowel syndrome and intestinal microbiota

Irritable bowel syndrome(IBS)is the most prevalent functional gastrointestinal disorder.It is a multifactoria disorder.Intestinal microbiota may cause the pathogenesis of IBS by contributing to abnormal gastrointestina motility,low-grade inflammation,visceral hypersensitivity,communication in the gut-brain axis,and so on.Previous attempts to identify the intestinal microbiota composition in IBS patients have yielded inconsistent and occasionally contradictory results.This inconsistency may be due to the differences in the molecular techniques employed,the sample collection and handling methods,use of single samples that are not linked to fluctuating symptoms,or other factors such as patients diets and phenotypic characterizations.Despite these difficulties,previous studies found that the intestina microbiota in some IBS patients was completely different from that in healthy controls,and there does appear to be a consistent theme of Firmicutes enrichment and reduced abundance of Bacteroides.Based on the differences in intestinal microbiota composition,many studies have addressed the roles of microbiotatargeted treatments,such as antibiotics and probiotics,in alleviating certain symptoms of IBS.This review summarizes the current knowledge of the associations between intestinal microbiota and IBS as well as the possible modes of action of intestinal microbiota in the pathogenesis of IBS.Improving the current level of understanding of host-microbiota interactions in IBS is important not only for determining the role of intestinal microbiota in IBS pathogenesis but also for therapeutic modulation of the microbiota.