基于巨噬细胞对肠黏膜愈合调控治疗炎症性肠病的药物研究现状

实现肠黏膜完整愈合是治疗炎症性肠病(inflammatory bowel disease,IBD)最理想的目标.患者肠黏膜愈合后不仅可以明显改变疾病进程、缓解临床症状,还能显著减免并发症发生、防止疾病复发.由于消化道溃疡损伤伴有慢性炎症是IBD主要病理特点,目前临床主要从抗炎入手治疗,但此类疗法不能很好地促进患者肠黏膜...     

慢性腹泻肠黏膜形态和通透性研究

目的探讨慢性腹泻患者肠黏膜形态和通透性的变化。方法对33例慢性腹泻患者和30名健康志愿者行结肠镜检查，并在镜下取回肠末端和回盲部黏膜各3块，光镜下观察肠黏膜的组织结构，同时测定尿中的乳果糖／甘露醇（L／M）比值，以评价肠黏膜屏障功能。结果慢性腹泻患者光镜下可见回肠末端有绒毛顶端上皮细胞水肿、脱落，但与健康志愿者差异无统计学意义（P〉0．05）；回盲部可见被覆上皮细胞明显水肿、脱落和破溃，甚至被覆上皮细胞成片完全脱落，与健康志愿者比较差异有统计学意义（P〈0。05）。慢性腹泻患者和健康志愿者尿L／M比值差异无统计学意义（P〉0．05）。结论慢性腹泻患者可能存在结肠黏膜屏障损害。     

辛伐他汀抑制大鼠炎症性肠病结肠纤维化结缔组织生长因子的表达

目的探讨大鼠炎症性肠病(IBD)结肠纤维化结缔组织生长因子(CTGF)的表达及辛伐他汀对其影响。方法 32只SD大鼠均分为对照组、IBD模型对照组、辛伐他汀低剂量(5mg/kg)和高剂量(20mg/kg)干预组。21d后观察结肠病理组织学变化;RT-PCR和Western blot检测结肠Ⅰ型胶原、CTGF mRNA和蛋白表达。结果与对照组相比,模型组结肠黏膜及黏膜下层见大量炎症细胞浸润,纤维组织增生,Ⅰ型胶原和CTGF表达增多(P<0.01)。辛伐他汀干预后,病理组织学较模型组改善,Ⅰ型胶原和CTGF表达明显下降(P<0.05)。结论 CTGF参与结肠炎大鼠肠纤维化形成,辛伐他汀可能通过抑制CTGF的表达减轻IBD肠纤维化进展。     

同型半胱氨酸调控MEK-ERK-MLCK通路影响结肠炎大鼠肠黏膜通透性的实验研究

目的探讨同型半胱氨酸(homocysteine,Hcy)是否通过调控MEK-ERK-MLCK通路影响结肠炎大鼠肠黏膜通透性的机制。方法 SD大鼠分为4组,A组为正常对照组(NS皮下注射+NS灌肠),B组为正常对照+Hcy注射组(Hcy皮下注射+NS灌肠),C组为TNBS模型组(NS皮下注射+TNBS灌肠),D组为TNBS模型+Hcy注射组(Hcy皮下注射+TNBS灌肠)。建立高Hcy血症的实验性结肠炎大鼠模型,实验结束时取大鼠结肠组织病理学检查,并进行结肠匀浆检测MPO活性,采用Western blot方法检测大鼠小肠组织中MEK、ERK、p-ERK、MLCK、p-MLCK的蛋白表达水平,采用RT-q PCR方法检测大鼠小肠组织中MLCK mRNA表达。结果与正常对照组及模型对照组相比,TNBS模型+Hcy皮下注射组大鼠DAI及HI评分增高,结肠匀浆MPO活性增高,小肠黏膜组织MEK、ERK、p-ERK、MLCK、p-MLCK蛋白表达水平增加,MLCK mRNA相对表达量增加。结论 Hcy增加实验性结肠炎大鼠肠黏膜通透性,可能与调控MEK-ERKMLCK信号通路有关。     

炎症性肠病的病因研究进展

炎症性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD).IBD的病因和发病机制尚未完全明确,近10年来倾向于认为肠道粘膜免疫系统异常反应所导致的炎症反应在IBD发病中起重要作用,另外还有其他多种因素相互作用共同导致,主要包括遗传和感染等方面.     

炎症性肠病的肠外表现及治疗

炎症性肠病(IBD)是一种系统性疾病,不仅累及肠道,亦可出现多种肠外表现(EIM),易造成误诊,及时诊断及合理治疗能够改善患者的功能状态和生活质量,现将IBD肠外表现及治疗方法作一综述。     

炎症性肠病的药物治疗

1什么是炎症性肠病？ 炎症性肠病（inflammatory bowel diseases,IBD）是一种特殊的慢性肠道炎症性疾病,主要包括克罗恩病和溃疡性结肠炎。克罗恩病可发生于消化道任何部位,为慢性、反复发作的肠壁全层性炎症,常见于回肠末端和结肠。溃疡性结肠炎为发生于结肠的弥漫性、浅表性、局限于黏膜层的炎症,常见于直肠和乙状结肠。     

自噬调节策略在炎症性肠病临床前研究中的进展

炎症性肠病(inflammatory bowel disease, IBD)是一种难治性肠道炎症性疾病,包括溃疡性结肠炎和克罗恩病,具有进行性且不可预测的病程特点。肠道炎症和免疫反应异常与IBD发病机制密切相关。自噬是细胞中重要的分解代谢过程,已被证明与包括IBD在内的多种炎症性疾病存在联系。本文从自噬功能障碍与IBD的关系出发,重点阐述了炎症小体抑制剂、肠道微生物群调节剂及其他信号调节剂等作用于肠上皮细胞和巨噬细胞的自噬调节剂在IBD中的研究进展。     

大黄素对肠黏膜屏障损伤的保护作用及机制研究

目的观察大黄素对大鼠肠缺血再灌注（IR）肠黏膜屏障功能的影响。方法 48只雄性SD大鼠,随机分为假手术（S）组、模型（IR）组、模型＋生理盐水（IRS）组和模型＋大黄素（IRE）组。IRE组给予40mg/（kg.d）大黄素灌胃,IRS组给予等量生理盐水灌胃,连续7 d,于第7天给药2 h后,制备肠缺血再灌注模型。光镜和透射电镜下分别观察各组小肠病理改变和紧密连接损伤,并进行Chiu’s评分。用TUNEL法检测肠黏膜细胞凋亡指数,Western Blot半定量法测定肠黏膜Claudin-1、Occludin蛋白含量。结果 IRE组与IR组、IRS组相比,小肠病理损伤和紧密连接结构破坏明显减轻,Chiu’s评分降低（P〈0.05）,细胞凋亡指数降低（P〈0.05）,两种连接蛋白Claudin-1、Occludin含量增加（P〈0.05）。结论大黄素可以缓解肠缺血再灌注造成的肠道损伤、减少肠黏膜细胞凋亡、保护肠上皮细胞间紧密连接,对肠黏膜屏障具有保护作用。     

PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease

Background and aimsInflammatory bowel disease (IBD) are the major risk factor for developing colitis associated cancer (CAC). Previously, we have reported that Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was overexpressed in colorectal cancer (CRC), but we don't know the role of PIK3R3 in IBD.MethodsWe investigated the differential expression of PIK3R3 and ZO-1 in IBD patients by using Immunohistochemical (IHC) and Gene Expression Omnibus (GEO) database analysis. Caco-2 cells were exposed to different conditions to assess protein level changes of PIK3R3 and ZO-1. Caco-2 cell monolayers were transfected with PIK3R3/siPIK3R3 to assess transepithelial electrical resistance. Tight junction protein integrity was assessed by immunoblot and immunofluorescence. For further, intestinal permeability and tight junction protein integrity were assessed in animal study to assess the treatment role of PIK3R3 specific inhibitor TAT-N 15 (N15).ResultsPIK3R3 was increased in IBD patients, and negatively controlled the expression of ZO-1. In vitro, PIK3R3 regulates ZO-1 by activating NF-kB pathway. Overexpression of PIK3R3 in Caco-2 cells decreased transepithelial electrical resistance (TEER), an opposite result was observed in siPIK3R3 cells. In animal study, inhibition of PIK3R3 by N15 contributed to amelioration of DSS-induced intestinal permeability. Mice treated with N15 exhibited less disruption of TJs in colon tissues.ConclusionsPIK3R3 was increased in clinical IBD patients with accompanying disruption of ZO-1 expression. Inhibition of PIK3R3 attenuated DSS-induced IBD symptoms in a mouse model. These findings indicated that PIK3R3 could be a therapeutic target for IBD.     

调节性T细胞与炎性肠病研究进展

炎性肠病(Inflammatory bowel disease,IBD)为非特异性炎症性肠病,主要包括溃疡性结肠炎(Ul-cerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。其病因和发病机制尚未完全明确。已知肠道粘膜免疫系统异常反应所导致的炎症反应在IBD中发挥着重要作用。笔者对调节性T细胞在肠道免疫系统中的作用与IBD的发病机制相关性的研究进展做一综述,为临床治疗IBD的新药研究提供可能性的途径。     

New developments in the pharmacotherapy of inflammatory bowel disease

In this article the clinical features and aetiology of inflammatory bowel diseases are described and current pharmacotherapeutic possibilities are explored. Also reviewed are recent developments and future prospects for the pharmacotherapy of inflammatory bowel diseases, including aminosalicylates, corticosteroids, immunosuppressants, lipoxygenase inhibitors, fish oil, sucralfate, bismuth compounds, free radical scavengers, (hydroxy)chloroquine, sodium cromoglycate and methotrexate.     

A new target for the treatment of inflammatory bowel disease: Interleukin-37

Interleukin (IL)-37 belongs to the IL-1 cytokine family. It has anti-inflammatory effects on numerous autoimmune diseases such as asthma, psoriasis, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA). Mechanistically, IL-37 plays an anti-inflammatory role by regulating the expression of inflammatory factors in two ways: binding extracellular receptors IL-18R or transferring into the nucleus with Smad3. IBD is a kind of idiopathic intestinal inflammatory disease with unknown etiology and pathogenesis. Recent researches had proved that IL-37 is negatively involved in the pathogenesis and development of IBD. Among various inflammatory diseases, IL-37 has been shown to regulate inflammatory development by acting on various immune cells such as neutrophils, macrophages (Mϕ), dendritic cells (DCs), T cells and intestinal epithelial cells. This review summarizes the biological role of IL-37, and its immunoregulatory effects on the immune cells, especially anti-inflammatory function in both human and experimental models of IBD.     

益生菌对炎症性肠病的治疗作用分析

目的：观察益生菌治疗炎症性肠病的临床效果。方法：选取本院160例炎症性肠病患者,将患者随机分为治疗组和对照组。对对照组患者进行单纯柳氮磺胺吡啶片治疗,对治疗组患者使用柳氮磺胺吡啶片联合益生菌治疗,对比治疗效果。结果：治疗组有效率达到92．5％,出现并发症1例;对照组有效率仅为75．0％,出现并发症4例。治疗组治疗效果明显好于对照组（P〈0．05）,两组差异具有统计学意义。结论：益生菌可以明显提升炎症性肠病治疗效果,改善临床控制有效率,值得临床推广。     

间充质干细胞在炎症性肠病治疗中的研究进展

现代医学研究表明炎症性肠病的发病机制与患者免疫失调具有密切关系。目前临床对于炎症性肠病治疗主要原则为消除活动性炎症以及改善免疫功能紊乱,比如氨基水杨酸制剂、免疫抑制剂以及糖皮质激素等均是临床治疗常用药物。间充质干细胞为具有自我复制以及多方向分化潜能的成体干细胞,对于组织修复以及免疫调节等均具有良好的治疗效果,目前在心肌梗死以及系统性红斑狼疮等疾病治疗中应用较为广泛。近些年很多专家将间充质干细胞应用于炎症性肠病的治疗中,取得了良好的效果。本文将这些新研究进展进行综述,以期为炎症性肠病的临床治疗提供借鉴。     

蜂胶在炎症性肠病中相关作用的研究进展

炎症性肠病（inflammatory bowel disease,IBD）包括克罗恩病和溃疡性结肠炎,以慢性复发性肠炎为主要特征。其发病原因目前尚未完全明确,并且缺乏有效的靶向药物,治愈难度很大。蜂胶（propolis）是一种具有多种生物学活性及药理学功效的天然混合物。相关研究表明,富含多酚的蜂胶提取物表现出显著的抗炎...     

Pharmacokinetics of intravenous methylprednisolone and oral prednisone in paediatric patients with inflammatory bowel disease during the acute phase and in remission

Objective: The present study was undertaken to evaluate the influence of inflammatory bowel disease on the pharmacokinetics of intravenous methylprednisolone and prednisolone (after oral administration of prednisone). Patients: Twelve children with inflammatory bowel disease, aged 12.3 years were studied during the active phase and in remission. In 6 patients the disease responded to oral prednisone while 6 did not respond. Methods: During the acute phase, intravenous methylprednisolone (2 mg · kg⁻¹) and oral prednisone (2 mg · kg⁻¹) were administered in a random order and blood was sampled over 48 h. Prednisone (2 mg · kg⁻¹) was readministered after remission. The concentrations of methylprednisolone and prednisolone were measured by high-pressure liquid chromatography. Results: During the acute phase, the systemic clearance of methylprednisolone was 0.98 (1 kg⁻¹ · h⁻¹) and the elimination half-life was 1.67 h. The area under the plasma concentration-versus-time curve of prednisolone was 4.00 and 3.20 · mg · h · l⁻¹ respectively during the active disease and remission, while its elimination half-life was 3.51 h during the acute phase and 2.42 h in remission. There were no pharmacokinetic differences between the patients who responded or did not respond to oral treatment. Conclusion: In children with inflammatory bowel disease, the initial response to corticosteroid therapy was not influenced by the pharmacokinetics of prednisolone and methylprednisolone. In addition, the pharmacokinetics of prednisolone was not modified by the inflammatory syndrome. Received: 5 December 1997 / Accepted in revised form: 14 April 1998     

The therapeutic potential of histamine receptor ligands in inflammatory bowel disease

In the intestine of patients suffering from inflammatory bowel disease concentrations of histamine are increased compared to healthy controls. Genetic ablation of histamine production in mice ameliorates the course of experimentally induced colitis. These observations and first pharmacological studies indicate a function of histamine in the pathogenesis of inflammatory bowel disease. However, a closer examination reveals that available data are highly heterogeneous, limiting the rational design of strategies addressing specific histamine receptor subtypes as possible target for pharmacological interaction. However, very recently first clinical data indicate that antagonism at the histamine receptor subtype H₄ provides a beneficial effect in at least the skin. Here, we discuss the available data on histamine effects and histamine receptor subtype functions in inflammatory bowel disease with a special emphasis on the histamine H₄-receptor.