microRNA和Th17细胞在炎症性肠病形成与发展中的作用

炎症性肠病(IBD)是一种慢性非特异性肠道炎症性疾病,其病因及发病机制至今尚未完全阐明.近年研究表明Th17细胞是影响IBD发生发展的关键因素之一,同时microRNA(miRNA)与Th17细胞间存在着密切联系,且miRNA在IBD患者肠黏膜组织及外周血中存在特异性表达.此文就miRNA、Th17细胞与IBD的形成、发展的关系作一综述.     

MicroRNA在炎症性肠病中的调控机制和临床应用

炎症性肠病(IBD)是一类慢性非特异性肠道炎性疾病,发病机制尚未明确。MicroRNA(miRNA)是一类内源性非编码RNA,在转录后水平调节目的基因表达。研究发现,miRNA参与对肠黏膜屏障和黏膜免疫系统的调控,miRNA表达异常与IBD的发生相关。本文就miRNA在IBD中的调控机制和临床应用作一综述。     

循环microRNA与炎症性肠病的研究进展

MicroRNA(miRNA)是一类具有调控功能的非编码RNA,作为转录后调控因子参与真核生物基因表达水平的调控。炎症性肠病(IBD)是一种慢性非特异性肠道炎性疾病,病因尚未完全明确。目前研究表明,循环miRNA在IBD患者体内存在特异性表达。本文就循环miRNA在IBD中的研究作一综述。     

FOXP3在炎症性肠病患者外周血和肠黏膜中的表达特点

背景：炎症性肠病（IBD）的发病与一系列免疫异常有关。免疫反应受特定的免疫调节细胞调控，包括CD4^＋CD25^＋T细胞．而CD4^＋CD25^＋T细胞的发育和功能可能受FOXP3基因调控。目的：研究FOXP3的表达特点以及IBD时FOXP3表达的改变。方法：以免疫磁珠分离CD4^＋、CD4^＋CD25^＋和CD4^＋CD25^-T细胞。以逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法检测IBD患者和非IBD对照外周血单个核细胞（PBMC）、肠固有层单个核细胞（LPMC）和肠黏膜组织中FOXP3的表达。结果：CD4^＋CD25^＋T细胞中FOXP3 mRNA的表达明显强于CD4^＋T细胞和未分离的PBMC或LPMC。T细胞受体（TCR）激活后，或经白细胞介素（IL）-2、IL-15作用后，PBMC或LPMC FOXP3 mRNA或蛋白表达明显增强。12例IBD中9例（75．0％）肠黏膜LPMC中检测到FOXP3 mRNA表达，高于对照肠黏膜的47．1％（8／17．P〉0．05）。未受刺激的IBD和对照肠黏膜组织中未检测到FOXP3 mRNA表达。结论：人类FOXP3的表达受T细胞活化影响。IBD患者肠黏膜LPMC中FOXP3 mRNA的表达率有增高的趋势．但与对照肠黏膜相比无显著差异．     

血红素加氧酶-1在炎症性肠病中的研究进展

血红素加氧酶（heme oxygenase．HO）是血红素降解过程中的限速酶．可将血红素降解为等摩尔的胆绿素、游离铁和一氧化碳（CO）。近年研究发现HO-1具有抗炎、抗凋亡、抗增生效应。炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD），其病因和发病机制尚未完全阐明。目前认为IBD主要系由免疫反应介导．并与遗传、环境因素密切相关。其特点之一是炎性细胞增多，炎性细胞因子表达增加。新近研究证实，HO-1的诱导表达对实验性结肠炎动物模型有重要保护作用，能减轻IBD由免疫系统活化所致的组织损伤，预示着HO-1在IBD的治疗中具有广泛应用前景。     

炎症性肠病患者血清和肠黏膜组织中miR-31-3p的表达水平及临床意义

目的 观察炎症性肠病（IBD）患者血清和肠黏膜组织中miR-31-3p的表达情况,并分析其在疾病诊断和病情评估中的应用价值。方法 随机选取2019年6月至2021年6月成都大学附属医院消化内科收治住院的符合纳入及排除标准的95例IBD患者（设为IBD组）,其中克罗恩病（CD）有33例（设为CD组）,溃疡性结肠炎（UC）有62例（设为UC组）;同期招募67名健康志愿者作为对照组。收集受试对象的肠黏膜组织及血清样本,采用实时荧光定量PCR技术检测血清和肠黏膜组织中miR-31-3p的表达水平,并分析其在IBD组与对照组,以及不同活动度IBD患者间的差异。采用Pearson相关系数法分析血清和肠黏膜组织中miR-31-3p的表达水平与IBD患者疾病活动度的相关性;采用ROC曲线分析血清和肠黏膜组织中miR-31-3p对IBD的诊断及病情评估的价值。结果 CD组和UC组患者血清和肠黏膜组织中miR-31-3p的表达水平均显著高于对照组（P<0.05）。轻度活动期、中度活动期、重度活动期的CD和UC患者血清和肠黏膜组织中miR-31-3p的表达水平均依次升高,组间比较差异均有统计学意义（P...     

MSCs-肠道菌群相互调控关系在IBD治疗中的作用

炎症性肠病(inflammatory bowel diseases,IBD)是一种慢性复发性非特异性肠道疾病,其病因和发病机制尚未完全阐明.研究证实肠道菌群与肠粘膜之间异常的免疫调控在IBD的发生发展中起着决定性作用,纠正菌群失调的肠道微生态疗法对IBD的治疗有着重要的临床意义.间充质干细胞(mesenchymal s...     

Toll样受体在炎症性肠病发病机制、并发症及治疗中的作用研究进展

炎症性肠病（IBD）是一种多因素导致的慢性非特异性自身免疫性疾病，发病机制复杂。Toll样受体（TLR）是模式识别受体，可诱导炎症反应。TLR在IBD中异常表达，在IBD的发生发展中占重要地位。TLR通过髓样分化因子（MyD88）依赖性通路和MyD88非依赖性通路影响肠黏膜屏障与免疫细胞分化，参与IBD的发生发展；TLR与IBD并发症密切相关，TLR下游炎症因子可促进肠纤维化，诱导炎症相关性结直肠癌，还可促进IBD患者血栓形成；临床可基于TLR基因多态性治疗IBD并判断预后，益生菌或内外源性调控物质可通过TLR通路改善IBD病情。     

大鼠炎症性肠病模型的建立与评价

炎症性肠病（IBD）是一类原因不明的慢性胃肠道疾病,免疫功能异常在IBD的发病过程中发挥重要作用已成共识,为进一步研究免疫异常致病的具体机制,建立理想的动物免疫致病模型对阐明该病的病因、病变发展规律以及有效的防治有重要意义,本实验拟用二硝基氯苯（DNCB）对中型大鼠造模,观察中型大鼠对DNCB的耐受性,探索最佳的DNCB用药浓度、剂量和作用时间.     

KIR2DL1和KIR2DL3在炎症性肠病患者外周血和肠组织中的表达

背景：KIR2DL1和KIR2DL3属抑制性杀伤细胞免疫球蛋白样受体家族成员,在一些免疫相关疾病中发挥重要作用.目前,KIR2DL1和KIR2DL3在炎症性肠病（IBD）中的研究还相对较少.目的：探讨KIR2DL1和KIR2DL3在IBD患者外周血和肠组织中的表达及其临床意义.方法：收集111例溃疡性结肠炎（UC）患者、101例克罗恩病（CD）患者和110例健康志愿者.以聚合酶链反应-序列特异性引物（PCR-SSP）法检测外周血中KIR2DL1和KIR2DL3表达,并分析其与患者临床特征的关系.以免疫组化染色检测肠组织中KIR2D L1蛋白表达.结果：UC组外周血KIR2DL1和KIR2DL3表型频率均显著低于正常对照组（P＜0.05）;CD组KIR2DL1表型频率显著低于正常对照组（P=0.026）,但两组KIR2DL3表型频率无明显差异（P＞0.05）.KIR2D L1和KIR2DL3表型频率与UC和CD患者的疾病活动性、病情严重程度和病变部位均无关.UC和CD患者肠组织中KIR2DL1蛋白表达均明显低于对照组（P＜0.001）.结论：IBD患者中存在KIR2DL1基因和蛋白的低表达,提示其在IBD的免疫发病机制中可能起重要作用.     

Role of the intestinal barrier in inflammatory bowel disease

A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. The single layer of intestinal epithelial cells （IECs） serves as a dynamic interface between the host and its environment. Cell polarity and structural properties of the epithelium is complex and is important in the development of epithelial barrier function. Epithelial cells associate with each other via a series of intercellular junctions. The apical most intercellular junctional complex referred to as the Apical Junction Complex （AJC） is important in not only cell-cell recognition, but also in the regulation of paracellular movement of fluid and solutes. Defects in the intestinal epithelial barrier function have been observed in a number of intestinal disorders such as inflammatory bowel disease （IBD）. It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of IBD. Thus, a better understanding of the intestinal epithelial barrier structure and function in healthy and disease states such as IBD will foster new ideas for the development of therapies for such chronic disorders.     

TGF-β in inflammatory bowel disease: a key regulator of immune cells,epithelium, and the intestinal microbiota

Inflammatory bowel disease (IBD) is defined as chronic intestinal inflammation, and includes ulcerative colitis and Crohn’s disease. Multiple factors are involved in the pathogenesis of IBD, and the condition is characterized by aberrant mucosal immune reactions to intestinal microbes in genetically susceptible hosts. Transforming growth factor-β (TGF-β) is an immune-suppressive cytokine produced by many cell types and activated by integrins. Active TGF-β binds to its receptor and regulates mucosal immune reactions through the TGF-β signaling pathway. Dysregulated TGF-β signaling is observed in the intestines of IBD patients. TGF-β signal impairment in specific cell types, such as T-cells and dendritic cells, results in spontaneous colitis in mouse models. In addition, specific intestinal microbes contribute to immune homeostasis by modulating TGF-β production. In this review, we describe the role of TGF-β in intestinal immunity, focusing on immune cells, epithelium, and intestinal microbes. In addition, we present potential therapeutic strategies for IBD that target TGF-β.

     

TL1A及其受体与炎症性肠病的研究进展

炎症性肠病(IBD)是病因不明的慢性非特异性肠道炎症性疾病,包括溃疡性结肠炎(UC)和克罗恩病(CD)。肿瘤坏死因子配体相关分子1A(TL1A)属肿瘤坏死因子(TNF)超家族成员,其受体包括死亡受体3(DR3)和诱骗受体3(DcR3)。近年研究发现,IBD肠黏膜TL1A及其受体表达异常可能与本病的发生相关。本文就TL1A及其受体与IBD相关性的研究进展作一综述。     

Chemokines in inflammatory bowel diseases

Uncontrolled activation of mucosal effector cells has been identified as the main pathogenic mechanism involved in the initiation and perpetuation of mucosal inflammation in inflammatory bowel diseases (IBD). The sustained activation of these cells leads to the aberrant production of various pro-inflammatory mediators, which co-ordinated action amplifies the inflammatory process. In this setting a network of tissue-specific chemoattractant cytokines (chemokines) and their corresponding receptors have been implicated as main contributors in the initiation and perpetuation of the inflammatory reaction in IBD. They are produced by a variety of inflammatory cells present in IBD lesions, as well as endothelial and epithelial cells. Chemokines not only control the multistep process of leukocyte adhesion to and migration across the endothelium, but also the release of lipid mediators and oxygen radicals from leukocytes, the modulation of tumorigenesis, release of matrix metalloproteinases and tissue fibrosis. Numerous data indicate that that intestinal chemokine expression is non-selectively up-regulated in IBD and correlates with disease activity. The development of selective inhibitors for chemokines or chemokine receptors, based on a more complete understanding of the immunopathogenic role of chemokines in intestinal inflammation, will be of great interest as potential novel therapeutic strategies in IBD.     

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Inflammatory bowel disease(IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. mi RNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific m RNAs for degradation or translational inhibition. mi RNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of mi RNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how mi RNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific mi RNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing mi RNAs as new biomarkers and as potential therapeutic targets in IBD.     

MicroRNAs in inflammatory bowel disease

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene and protein expression. miRNAs are critical to a normal immune response and have altered expression in multiple immune-mediated disorders. This emerging role of miRNAs in the pathogenesis of multiple disease states has led to investigations into miRNA expression profiles in inflammatory bowel disease (IBD). The discovery of miRNAs in IBD is likely to contribute to our understanding of IBD pathogenesis and lead to clinical advances in IBD. This review focuses on miRNA expression in inflammation, autoimmune disorders, and inflammation-associated cancer, as well as their function in the biology and management of IBD.     

Gut microbiota in the pathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic and relapsing inflammatory disorder of the intestine. Although its incidence is increasing globally, the precise etiology remains unclear and a cure for IBD has yet to be discovered. The most accepted hypothesis of IBD pathogenesis is that complex interactions between genetics, environmental factors, and the host immune system lead to aberrant immune responses and chronic intestinal inflammation. The human gut harbors a complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. The gut microbiota has physiological functions associated with nutrition, the immune system, and defense of the host. Recent advances in next-generation sequencing technology have identified alteration of the composition and function of the gut microbiota, which is referred to as dysbiosis, in IBD. Clinical and experimental data suggest dysbiosis may play a pivotal role in the pathogenesis of IBD. This review is focused on the physiological function of the gut microbiota and the association between the gut microbiota and pathogenesis in IBD. In addition, we review the therapeutic options for manipulating the altered gut microbiota, such as probiotics and fecal microbiota transplantation.     

Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2

Toll-like receptors (TLR) and NOD2 are emerging as key mediators of innate host defence in the intestinal mucosa, crucially involved in maintaining mucosal as well as commensal homeostasis. Recent observations suggest new (patho-) physiological mechanisms of how functional versus dysfunctional TLRx/NOD2 pathways may oppose or favour inflammatory bowel disease (IBD). In health, TLRx signalling protects the intestinal epithelial barrier and confers commensal tolerance whereas NOD2 signalling exerts antimicrobial activity and prevents pathogenic invasion. In disease, aberrant TLRx and/or NOD2 signalling may stimulate diverse inflammatory responses leading to acute and chronic intestinal inflammation with many different clinical phenotypes.     

肠道菌群在炎症性肠病发生中的作用

炎症性肠病（IBD）是一种慢性非特异性肠道炎症性疾病．其明确病因和发病机制至今仍不清楚。近年来随着微生态学的发展．肠道菌群与IBD发病的关系日益受到关注。多项证据表明IBD患者存在肠道菌群紊乱。本文就肠道菌群在IBD发生中作用的研究进展作一综述。