炎症性肠病动物模型研究进展

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）。目前IBD的确切病因和发病机制尚不清楚。相当一部分IBD的研究成果源于动物模型的研究,因此建立合适的动物模型至关重要。本文就几种常用的IBD实验动物模型作一综述。     

Current Advantages in the Application of Proteomics in Inflammatory Bowel Disease

Since the formulation of the concept of proteomics, a plethora of proteomic technologies have been developed in order to study proteomes. In inflammatory bowel disease (IBD), several studies use proteomics to try to better understand the disease and discover molecules which can be used as biomarkers. Biomarkers should be able to be used for diagnosis, therapy and prognosis. Although several biomarkers have been discovered, few biomarkers have clinical value. In this review, we analyze and report the current use of proteomic techniques to highlight biomarkers characterizing IBD, and different stages of disease activity. We also report the biomarkers and their potential clinical value.     

正确选择炎症性肠病实验研究的动物模型

炎症性肠病（inflammatory bowel disease，IBD）是一种反复发作的慢性非特异性肠道炎症性疾病。主要包括溃疡性结肠炎（ulcerative colitis，UC）和克罗恩病（Crohn’s disease，CD）。其确切病因和发病机制至今尚未阐明，治疗上也缺乏特异有效的药物旧。因此，为研究其病因和发病机制以及开发新的治疗药物．建立理想的、类似于人类IBD的动物模型就显得非常重要。理想的IBD实验动物模型应具备如下特点：①肠道炎症的发生、病程、病理和病理生理学改变与人类IBD相同或相似；②实验动物具有明确的遗传背景：③以已知抗原易于诱导免疫反应；④传统IBD治疗药物治疗有效；⑤实验动物在没有遗传或化学药物干预的情况下。常能自发形成肠道炎症。然而，实际上很少有如此理想的动物模型。应当明确的是，目前所建立的所有IBD动物模型都不是真正意义上的IBD动物模型．而只能称为肠道炎症模型。     

The Implications of Oxidative Stress and Antioxidant Therapies in Inflammatory Bowel Disease: Clinical Aspects and Animal Models

Inflammatory bowel disease (IBD), including Crohn''s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patient''s immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.Key Words: Animal models, antioxidants, Crohn''s disease, lipid peroxidation, reactive oxygen species, ulcerative colitis     

Urinary 8-Hydroxydeoxyguanosine Excretion as a Non-Invasive Marker of Neutrophil Activation in Animal Models of Inflammatory Bowel Disease

Background: Because free radicals contribute to ulcerative colitis and Crohn's disease, assessing oxidative load in vivo could provide a surrogate marker of inflammation and disease status. Methods: Electrochemical high-performance liquid chromatography was used to study urinary excretion of 8-hydroxydeoxyguanosine (8-OH-dGUA), formed by reaction of hydroxyl radicals with native DNA, in 2,4,6-trinitrobenzene-sulfonic acid (TNBS) and dextran sulfate (DSS) rat models of bowel inflammation. Bowel myeloperoxidase (MPO) and histopathology were also assessed. Results: TNBS enema (75 mg/kg in 50% ethanol) and oral DSS (6% via drinking water) both yielded an inflammatory response reflected by increases in bowel MPO that were significantly correlated with tissue injury. In both models urinary 8-OH-dGUA excretion was significantly correlated with bowel MPO activity and epithelial injury and remained at control levels when neutrophils (PMN) were eliminated, whereas epithelial injury and crypt erosion persisted despite neutropenia. Conclusions: Urinary 8-OH-dGUA excretion directly reflects PMN activation in vivo, thereby providing a non-invasive surrogate marker for inflammation in these models which is more indicative of PMN activation than either MPO activity, which does not distinguish inactive from active MPO, or epithelial status, which is independent of PMN activation in both models.     

Osteoporosis in Inflammatory Bowel Disease

Osteoporosis commonly afflicts patients with inflammatory bowel disease, and many factors link the 2 states together. A literature review was conducted about the pathophysiology of osteoporosis in relation to inflammatory bowel disease. Screening guidelines for osteoporosis in general as well as those directed at patients with inflammatory bowel disease are reviewed, as are currently available treatment options. The purpose of this article is to increase physician awareness about osteopenia and osteoporosis occurring in patients with inflammatory bowel disease and to provide basic, clinically relevant information about the pathophysiology and guidelines to help them treat these patients in a cost-effective manner.     

Atopy in Inflammatory Bowel Disease

Thirty-nine patients with ulcerative colitis and 35 with Crohn's disease have been investigated for evidence of reaginic hypersensitivity and compared with control subjects. There was no difference in the frequency of a personal or family history of atopy or in serum IgE levels. Similarly, no overall difference was noted in prick test responses to 21 allergens. However, further analysis of prick test responses showed that patients with inflammatory bowel disease responded more frequently to food allergens. This was highly significant when compared with healthy controls (p < 0.001). The relevance of this finding to the aetiology of inflammatory bowel disease is discussed.     

Inflammatory Bowel Disease in Kuwait

Inflammatory bowel disease is considered to be rare or nonexistent in some Arab countries. During a period of 6 years, 91 patients with ulcerative colitis and 17 with Crohn's disease were seen for initial diagnosis in the Gastroenterology Department of Amiri Hospital, which serves 55% of the population of Kuwait. From this group, 43 patients with ulcerative colitis and 14 patients with Crohn's disease were followed up for an average of 30.9 months. In the remaining 51 patients, the diagnosis was established in the same manner as in this series, hut these patients were sent back to the referring physicians and therefore were not available for follow-up. The severity of the disease in the majority of patients with ulcerative colitis was mild to moderate. Nine of 14 patients with Crohn's disease underwent surgery as a diagnostic procedure in an acute abdominal emergency or for treatment of complications. The duodenum was involved in two patients with Crohn's disease and the endoscopic picture and histology of these were initially interpreted as immunoproliferative small intestinal disease which is highly prevalent in this area. We suggest that the assumption that inflammatory bowel disease is uncommon in our population is wrong.     

炎症性肠病的抗生素治疗

炎症性肠病（IBD）主要包括克罗恩病（CD）和溃疡性结肠炎（UC）,近年越来越多的证据提示肠道细菌在其发病中发挥重要作用.虽然目前尚未发现特异性细菌与IBD的发病相关,但随着现代微生物学的发展以及肠道细菌与IBD研究的进展,发现肠道细菌可能是参与IBD始动和持续的因素.因此,采用抗生素治疗IBD可能是一种有效的治疗措施.本文就抗生素对活动期CD,CD肛周病变、CD术后复发以及活动期UC和囊袋炎的疗效作一综述.     

Refractory Inflammatory Bowel Disease

Opinion statement Therapeutic options for refractory colonic inflammation in patients with ulcerative colitis or Crohn’s disease have recently been augmented by the introduction of biologic therapies. Intravenous corticosteroids and cyclosporin A remain the standard therapies for severe ulcerative colitis. Monoclonal antibodies directed at tumor necrosis factor alfa (TNF-α) have proven to be most efficacious in patients with severe or refractory Crohn’s disease. Immunomodulatory therapy with azathioprine, 6-mercaptopurine, or methotrexate has demonstrated efficacy for maintenance of remission in patients with refractory ulcerative colitis or Crohn’s disease. The use of experimental biologic agents may be considered for those patients who fail to respond to or remain dependent on corticosteroids. Surgical intervention is indicated for patients with severe colitis who fail to respond to medical therapy or develop life-threatening complications such as perforation or toxic megacolon.