药物遗传学：药效学方面

个体间差异在药代动力学方面的认识已逾百年，但在药效学方面相应的认识却比较短暂。药物遗传学在药效学方面表现出两种不同的基本机制，一个是作为疾病异质性反应的Ⅰ型药物遗传学，另一个是作为疾病－病因学非相关的个体间差异反应的Ⅱ型药物遗传学，药物遗传学的药效学方面，对于认识临床药物反应，指导药物研发及临床实践将会发挥越来越重要的作用。     

药物遗传学在评价药物安全性和降低药物副作用中的作用

在美国,药物副作用位居死亡原因前列,一个重要原因,即现存的药物开发体系难以提供保证安全和疗效的适当信息。药物遗传学旨在研究药物反应中个体差异的遗传基础,本文概述药物遗传学的最新进展及其与代物安全性评价和个体化用药的关系。     

炎症性肠病和肠易激综合征相关性研究进展

炎症性肠病(IBD)是一组病因未明的慢性肠道炎症性疾病,一般指溃疡性结肠炎(UC)和克罗恩病(CD)。肠易激综合征(IBS)是一种临床常见的胃肠功能紊乱性疾病。一般来说两种疾病发病机制、临床表现及预后均不相同。但近年发现,     

一氧化氮与炎症性肠病

炎症性肠病（IBD）为慢性复发性肠道疾病,包括溃疡性结肠炎（UC）与克罗恩病（CD）,发病可能与一氧化氮（NO）有关,NO对IBD一方面产生破坏作用,另一方面发挥保护作用,本文就NO与IBD的关系作一综述。     

炎症性肠病和肠易激综合征相关性研究进展

炎症性肠病(IBD)是一组病因未明的慢性肠道炎症性疾病,一般指溃疡性结肠炎(UC)和克罗恩病(CD).肠易激综合征(IBS)是一种临床常见的胃肠功能紊乱性疾病.一般来说两种疾病发病机制、临床表现及预后均不相同.但近年发现,IBD患者发病早期、缓解期、或仅表现为腹痛及排便习惯的改变时,经常与IBS发生混淆,且两者在发病机制方面具也有一定的相似性.本文就IBD与IBS的相似性表现综述如下.     

250例炎症性肠病住院病人临床分析

目的探讨炎症性肠病(Inflammatoryboweldisease,IBD)的临床特点。方法回顾性分析我院14年来确诊的IBD住院病人250例。结果161例溃疡性结肠炎(Ulcerativecolitis,UC)及89例克罗恩病(Crohn'sdisease,CD)中,均男多于女(1.3～1.9:1),各年龄段均有发病,发病高峰为20～50岁。1%CD有阳性家族史。70%～80%UC患者有腹痛、腹泻、血便和黏液便;UC病变范围分型为直肠炎27例(18%),直肠乙状结肠炎40例(26%),左半结肠炎29例(19%),全结肠炎52例(34%),区域性结肠炎4例(3%);病情轻、中、重度分别为67例(42%)、59例(37%)、35例(21%);临床类型为暴发型5例(3%),初发型68例(42%),慢性持续型35例(22%),慢性复发型53例(33%)。58%～80%CD患者有腹痛腹泻,28%CD病人有血便;CD病变范围分型为小肠型28例(31%)、结肠型30例(34%)、回结肠型27例(30%)、其他(食道、十二指肠)4例(5%);病情轻、中、重度分别为15例(17%)、28例(31%)、46例(52%);疾病表型为非狭窄非穿孔型25例(28%),狭窄型33例(37%),穿孔型31例(35%)。肠外表现多累及关节、口腔、皮肤和眼,UC及CD发病率分别为2%、0.6%、0、0和6%、5%、5%、1%。CD并发症较多,主要为肠梗阻、瘘管及穿孔。12例(7%)UC病人因内科治疗无效而行手术,42例(47%)CD病人是经手术确诊为CD,其中13例(15%)初诊为“阑尾炎”。结论IBD就诊人数逐年增加。IBD临床表现多样,CD肠外表现及并发症较UC多见,误诊率较高。     

炎症性肠病内科护理体会

<正>炎症性肠病是一组病因不明的慢性肠道炎症性疾病,包括溃疡性结肠炎和克隆病,以及未定型的结肠炎。目前IBD的病因和发病机制仍不清楚,可能与遗传感染和精神因素有关,以其难治性和反复发     

炎症性肠病治疗进展

炎症性肠病(Inflammatory bowel disease，IBD)是一组病因不明的慢性、反复发作性肠道非特异炎症性疾病，主要包括溃疡性结肠炎(ulcerative colitis，UC)和克罗恩病(Crohn’S disease，CD)，发病率在我国乃至亚洲地区呈增高趋势，日前的主要治疗方法是抗炎和调节免疫反应：近年来随着对IBD发病机制的深入研究，许多全新的治疗方法和新型的药物制剂开始应用于临床。现就IBD的治疗进展情况作一综述。     

炎症性肠病的药物治疗现状

炎症性肠病（inflammatory bowel disease,IBD）目前是消化系统疾病的研究热点之一,主要包括溃疡性结肠炎（ulcerative colitis,UC）和克罗恩病（Crohn''s disease,CD）,其发病机制尚未完全阐明,也尚无针对IBD的有效治疗药物。随着对IBD发病机制的深入研究,出现了一些新型药物和制剂。笔者就IBD及其药物治疗的研究现状作一简要综述。     

Safety and Efficacy of Biologic Agents for the Management of Inflammatory Bowel Disease After Liver Transplantation

Primary sclerosing cholangitis (PSC) frequently progresses to end‐stage liver disease and cirrhosis, requiring liver transplantation. Approximately 70% of patients with PSC have concomitant inflammatory bowel disease (IBD) during their clinical course. After liver transplantation for PSC, corticosteroids and other high‐intensity immunosuppressants are initiated to keep IBD in remission. Patients with IBD that is refractory to these agents may need to be managed with biologic therapies. Biologic agents, however, may further increase the risks for malignancy and infection due to their immunosuppressive effects. Thus, to gain a better understanding of the risks and benefits of these agents in this high‐risk patient population, we performed a literature search of the PubMed database (2002–2017) to identify studies assessing the efficacy and safety of various biologic agents for the management of IBD in liver transplant recipients. No randomized controlled studies or retrospective comparative studies were identified; however, 15 case reports and case series were identified that met our inclusion criteria. From these case reports, we identified 67 patients who developed de novo or recurrent IBD after liver transplantation and received anti–tumor necrosis factor‐α or anti‐integrin therapy. Of the 13 published cases reporting clinical response or remission of IBD activity in liver transplant recipients (59 patients), clinical response or remission of IBD was reported in 38 (64.4%) of those patients. Adverse complications reported included cholangitis, oral candidiasis, Clostridium difficile colitis, bacterial pneumonia, cryptosporidiosis, Epstein–Barr virus–positive posttransplantation lymphoproliferative disease, and hepatotoxicity. Given the limited literature (case reports and case series) highlighted in this review, biologic agents such as tumor necrosis factor‐α inhibitors and integrin inhibitors commonly used for moderate to severe IBD may be appropriate after liver transplantation; however, consideration of risk versus benefit should always occur in a patient‐specific manner.     

基于网络药理学的五味子治疗炎性肠病机制研究

目的：对五味子进行网络药理学研究,阐明其治疗炎性肠病的有效活性成分及潜在靶点。方法：通过生物学信息数据库预测五味子活性成分的潜在作用靶点,采用Cytoscape软件构建五味子的“成分-靶点-通路”网络模型。结果：五味子中8种成分与17个靶点具有潜在相互作用,涉及神经配体相互作用及TNF信号通路在内的多个生物过程,对炎性肠病起到治疗作用。结论：通过与炎性肠病靶点的关联筛选,结合分子对接验证,发现五味子可通过多种信号通路发挥治疗炎性肠病的作用,PTGS1（COX-1）、PTGS2（COX-2）是五味子各活性成分中作用较多的调节靶点,当归酰戈米辛O对这两个靶点的作用较强。     

肠道菌群在炎症性肠病发病机制与治疗中的作用研究进展

炎症性肠病是一种以肠道炎症和黏膜损伤为特征的慢性疾病,主要包括克罗恩病和溃疡性结肠炎,其发病原因尚不明确。现有研究表明炎症性肠病的发病机制与宿主的遗传易感性、肠道菌群紊乱、肠黏膜屏障破坏和肠黏膜免疫异常等密切相关。总结目前炎症性肠病发病机制、患者肠道菌群结构及治疗方法等相关的研究进展,旨在对今后炎症性肠病的治疗和药物研发有所裨益。     

中文版Morisky服药依从性评估量表在炎症性肠病患儿中应用的信效度评价

目的 探讨中文版Morisky服药依从性量表(包括监护人版和未成年人版)在炎症性肠病患儿中应用的信度与效度,并明确炎症性肠病患儿服药依从性现状与特征。方法 纳入炎症性肠病患儿141例,以中文版Morisky量表为评估工具,以现场发放与回收问卷的形式收集数据,采用克伦巴赫(Cronbach's)a 系数和因子分析分别评价量表内部一致性信度和结构效度,采用Spearman检验评估患儿服药依从性与其疾病严重程度的相关性。结果 监护人版和未成年人版Morisky量表的Cronbach's a系数分别为0.701和0.738;因子分析结果共提取3个公因子,累积方差贡献率分别为67.94%和72.24%;141例患儿的用药依从性评估得分为6.75(4.75,8.0)分,其中,依从性不良、中等与极好的患儿分别为58例(41.1%),39例(27.7%)和44例(31.2%);患儿用药依从性得分与其疾病严重程度呈显著负相关关系(R_s=-0.286,P=0.001)。结论 中文版未成年人版和监护人版Morisky量表均具有较好的信度与效度,可用于评估炎症性肠病患儿的服药依从性。近一半炎症性肠病患儿服药依从性差,忘记服药是影响依从行为的主要障碍,且患儿用药依从性与其疾病严重程度呈显著负相关,临床应予以高度重视。     

核酸药物及其给药系统用于炎症性肠病治疗的研究进展

炎症性肠病是一种常见的免疫功能紊乱所致慢性顽固性胃肠道炎性疾病,现有的治疗手段难以根治。随着炎症性肠病分子机制研究的不断深入,在基因水平上应用核酸药物及其给药系统,对炎症性肠病发挥的独特治疗作用,已受到越来越多的关注,并取得一定进展。本文简介炎症性肠病的发病机制,综述近年来核酸药物及其给药系统用于炎症性肠病治疗的研究进展。     

Metabolic and Pharmacological Properties of Rutin,a Dietary Quercetin Glycoside,for Treatment of Inflammatory Bowel Disease

Purpose Orally administered rutin reportedly ameliorates 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis of rats. We investigated the metabolic and pharmacological properties of rutin underlying the rutin-mediated amelioration of the rat colitis.Methods Apparent partition coefficients of rutin and its aglycone quercetin were compared. The biochemical/chemical stability of rutin was examined in the contents of various segments of gastrointestinal tracts of rats. Inflammatory indices were determined in the colitis rats after oral administration of rutin or rectal administration of quercetin. In human colon epithelial cells, the effect of quercetin on tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa B (NFκB) activation was examined.Results The sugar residue in rutin greatly lowered the apparent partition coefficient and was rapidly deglycosylated to liberate quercetin in the cecal contents, whereas it was stable in the contents of the upper intestine. Not only oral administration of rutin but also rectal administration of quercetin remarkably ameliorated TNBS-induced colitis rats, indicating that quercetin liberated from rutin is therapeutically active. Furthermore, quercetin dose-dependently inhibited an inflammatory signal TNF-α-dependent NFκB activation.Conclusions Our data suggest that rutin acted as a quercetin deliverer to the large intestine and its anti-inflammatory action in TNBS-induced colitis rats may be through quercetin-mediated inhibition of TNF-α-induced NFκB activation.     

CD40在大鼠炎症性肠病外周血和结肠组织中的表达

目的：研究CD40在炎症性肠病（IBD）大鼠外周血和结肠组织单一核细胞（MC）中的表达及其与IL-12的相关性.方法：利用流式细胞仪检测CD40在14只炎症性肠病大鼠（模型组）和16只正常大鼠（对照组）外周血和肠组织MC上的表达,并用ELISA法检测IL-12.结果：模型组外周血、结肠组织MC中CD40阳性细胞百分数和IL-12较对照组高（P＜0.05）.结肠MC中CD40与IL-12呈正相关（r=0.845,t=12.5,P＜0.05）.结论：IBD大鼠存在CD40与IL-12表达的异常,且两者有内在的联系.     

炎症性肠病治疗药物研究进展

炎症性肠病（IBD）,IBD至少包括克罗恩病和溃疡性结肠炎两种独立疾病。IBD对人体健康带来极大的损害,严重影响了生活质量,加重患者的经济负担。本文主要对IBD的流行病学、致病因素以及临床治疗药物进行了总结,期望能为后续IBD的药物研发和治疗提供参考。     

A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents

Ulcerative colitis and Crohn''s disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD.