炎症性肠病动物模型的研究概况

The etiology and pathogenesis of inflammatory bowel disease are up to now still not clear and definite. Establishing the ideal animal model to study its cause and pathogenesis of this disease is very important. The ideal animal model should have the same manifestation with human inflammatory bowel disease on clinical and pathologic feature etc. In this article, the method, the pathologic character isfics and concerning pathogenesis, of a few common useful experiment animal models are discussed.     

Molecular crosstalk of probiotic bacteria with the intestinal immune system: Clinical relevance in the context of inflammatory bowel disease

It is current knowledge that the intestinal microbiota plays a major role in the development and maintenance of intestinal health. Intestinal epithelial cells (IEC) constitute the interface between the gut lumen and the innate and adaptive immune system. To maintain intestinal homeostasis, the organized and diffuse compartments of the gut-associated lymphoid tissue have to process the continuously varying information at the interface between the luminal side and the host. Dysregulated intestinal immune responses towards commensal bacteria are an important factor in the pathogenesis of inflammatory bowel diseases (IBD). In contrast to the colitogenic effects of enteric bacteria, clinical and experimental studies showed that specific probiotic strains are protective in the context of chronic intestinal inflammation. Although the molecular understanding of bacteria-host interaction is improving, the anti-inflammatory mechanisms induced by these probiotic bacteria are just starting to be unraveled. The present review is meant to summarize and discuss the clinical relevance of probiotics, but it also seeks to give an overview about currently known probiotic mechanisms in the context of chronic intestinal inflammation with a focus on IEC.     

The human gastrointestinal tract and oral microbiota in inflammatory bowel disease: a state of the science review

Inflammatory bowel disease (IBD) includes a spectrum of diseases from ulcerative colitis (UC) to Crohn's disease (CD). Many studies have addressed the changes in the microbiota of individuals affected by UC and CD. A decrease in biodiversity and depletion of the phyla Bacteroidetes and Firmicutes has been reported, among others. Changes in microbial composition also result in changes in the metabolites generated in the gut from microbial activity that may involve the amount of butyrate and other metabolites such as H₂S being produced. Other factors such as diet, age, or medication need to be taken into consideration when studying dysbiosis associated with IBD. Diverse bacterial species have been associated specifically or non‐specifically to IBD, but none of them have been demonstrated to be its ethiological agent. Recent studies also suggest that micro‐eukaryotic populations may also be altered in IBD patients. Last, but not least, viruses, and specially bacteriophages, can play a role in controlling microbial populations in the gastrointestinal tract. This may affect both bacterial diversity and metabolism, but possible implications for IBD still remain to be solved. Dysbiosis in the oral microbiome associated with IBD remains an emerging field for future research.     

同型半胱氨酸与炎症性肠病相关性血栓疾病的研究现状

目的 探讨同型半胱氨酸(Hcy)对炎症性肠病(IBD)患者的影响,为IBD相关性血栓疾病的深入研究提供参考.方法 在PubMeb、Medline、EMbase、CNKI、CBM数据库中检索1993年1月-2013年12月关于Hcy与IBD相关性血栓疾病的研究成果,进行分析总结.结果 IBD患者因反复炎症活动及高凝状态,增加了血栓形成的风险.高同型半胱氨酸血症(HHcy)在IBD相关性血栓疾病损伤机制中,主要通过氧化损伤血管内皮和体内抗凝系统失衡参与IBD相关性血栓形成的病理生理过程.HHcy是血栓形成的独立危险因素之一.结论 IBD患者血栓形成是一个复杂的病理过程,受多因素影响.Hcy在IBD相关性血栓疾病损伤机制中具有重要作用,其确切机制有待进一步研究.     

The Role of Fecal Calprotectin in Investigating Inflammatory Bowel Diseases

INTRODUCTION:

Invasive and non-invasive tests can be used to evaluate the activity of inflammatory bowel diseases.

OBJECTIVE:

The aim of the present study was to investigate the role of fecal calprotectin in evaluating inflammatory bowel disease activity and the correlation of fecal calprotectin with the erythrocyte sedimentation rate and C reactive protein values in inflammatory bowel disease.

METHOD:

Sixty-five patients affected with inflammatory bowel disease were enrolled. Twenty outpatients diagnosed with inflammatory bowel disease comprised the control group.

RESULTS:

In the present study, all patients in the control group had an fecal calprotectin value lower than the cut-off point (50 mg/kg).

CONCLUSION:

In conclusion, fecal calprotectin was found to be strongly associated with colorectal inflammation indicating organic disease. Fecal calprotectin is a simple and non-invasive method for assessing excretion of macrophages into the gut lumen. Fecal calprotectin values can be used to evaluate the response to treatment, to screen asymptomatic patients, and to predict inflammatory bowel disease relapses.     

Animal models in the investigation of anorexia

Anorexia nervosa (AN) is an eating disorder of unknown origin that most commonly occurs in women and usually has its onset in adolescence. Patients with AN invariably have a disturbed body image and an intense fear of weight gain. There is currently no definitive treatment for this disease, which carries a 20% mortality over 20 years. Development of an appropriate animal model of AN has been difficult, as the etiology of this eating disorder likely involves a complex interaction between genetic, environmental, social, and cultural factors. In this review, we focus on several possible rodent models of AN. In our laboratory, we have developed and studied three different mouse models of AN based on clinical profiles of the disease; separation stress, activity, and diet restriction (DR). In addition, we discuss the spontaneous mouse mutation anx/anx and several mouse gene knockout models, which have resulted in an anorexic phenotype. We highlight what has been learned from each of these models and possibilities for future models. It is hoped that a combination of the study of such models, together with genetic and clinical studies in patients, will lead to more rational and successful prevention/treatment of this tragic, and often fatal, disease.     

Animal models of mucosal inflammation and their relation to human inflammatory bowel disease

Animal models of inflammatory bowel disease (IBD) have been useful in the identification of those immune responses uniquely involved in IBD pathogenesis and in defining the important roles of environmental influences, such as normal luminal bacterial flora and the genetic composition of the host, in modifying IBD-associated inflammation. Recent studies have focused particular attention on CD4+ T cells which produce excessive quantities either of Th1 cytokines (IFN-gamma and TNF) directed by IL-12 or of a Th2 cytokine (IL-4), relative to the production of suppressive cytokines such as IL-10 and transforming growth factor beta. Such insights will be extremely beneficial in the development of novel approaches to the control of IBD-type inflammation, such as the use of anticytokine therapies and gene therapy, and finally, in the identification of the genetic abnormalities and the antigens driving the inflammation that underlies the human disease.     

Anti-inflammatory effects of probiotic yogurt in inflammatory bowel disease patients

Our aim was to assess anti-inflammatory effects on the peripheral blood of subjects with inflammatory bowel disease (IBD) who consumed probiotic yogurt for 1 month. We studied 20 healthy controls and 20 subjects with IBD, 15 of whom had Crohn's disease and five with ulcerative colitis. All the subjects consumed Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 supplemented yogurt for 30 days. The presence of putative regulatory T (T(reg)) cells (CD4(+) CD25(high)) and cytokines in T cells, monocytes and dendritic cells (DC) was determined by flow cytometry from peripheral blood before and after treatment, with or without ex vivo stimulation. Serum and faecal cytokine concentrations were determined by enzyme-linked immunosorbent assays. The proportion of CD4(+) CD25(high) T cells increased significantly (P = 0.007) in IBD patients, mean (95% confidence interval: CI) 0.84% (95% CI 0.55-1.12) before and 1.25% (95% CI 0.97-1.54) after treatment, but non-significantly in controls. The basal proportion of tumour necrosis factor (TNF)-alpha(+)/interleukin (IL)-12(+) monocytes and myeloid DC decreased in both subject groups, but of stimulated cells only in IBD patients. Also serum IL-12 concentrations and proportions of IL-2(+) and CD69(+) T cells from stimulated cells decreased in IBD patients. The increase in CD4(+) CD25(high) T cells correlated with the decrease in the percentage of TNF-alpha- or IL-12-producing monocytes and DC. The effect of the probiotic yogurt was confirmed by a follow-up study in which subjects consumed the yogurt without the probiotic organisms. Probiotic yogurt intake was associated with significant anti-inflammatory effects that paralleled the expansion of peripheral pool of putative T(reg) cells in IBD patients and with few effects in controls.     

H.polygyrus感染对T细胞介导的炎症性肠病的影响及其作用机制研究

目的: 研究多形螺旋线虫(H. polygyrus)感染对CD4⁺辅助性T细胞介导的小鼠炎症性肠病(IBD)的影响及其作用机制。方法: 用卵清蛋白(OVA)特异性的CD4⁺辅助性T细胞转入重度联合免疫缺陷(SCID)小鼠中制作IBD模型。将IBD小鼠感染H. polygyrus,14 d后处死小鼠,观察结肠的组织学变化,用ELISA法和流式细胞术检测肠系膜淋巴结中干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)的表达。另外,对感染H. polygyrus的IBD小鼠注射IL-4单克隆抗体以阻断IL-4的分泌,9 d后处死小鼠,观察相同的指标。结果: 与无感染组相比,感染H. polygyrus的IBD小鼠结肠病损明显加重,肠系膜淋巴结中IL-4水平明显增高,IFN-γ水平明显降低(均P<0.05)。在IL-4阻断实验中,与无IL-4阻断组相比,IL-4阻断组结肠病损明显减轻,IL-4水平明显降低,IFN-γ水平明显增高(均P<0.05)。结论: H. polygyrus感染在CD4⁺ T细胞介导的IBD模型早期加重了炎症反应,其作用可能是通过诱导Th2细胞因子的分泌、抑制Th1细胞因子的分泌来实现的,提示用蠕虫治疗IBD时需谨慎。     

A web-based patient education system and self-help group in Persian language for inflammatory bowel disease patients

BACKGROUND AND AIMS: To study the use patterns of a Persian web-based patient education system for inflammatory bowel disease (IBD) patients in Iran. METHODS: A web-based patient education system was developed with Persian content in three sections: general, ulcerative colitis (UC), and Crohn's disease (CD). The website included a forum for patients to communicate as a self-help group. A customized web tracking system recorded web use statistics. Polls at the bottom of each page collected the visitors' opinion on the extent of helpfulness and readability of page contents. Web use data were analyzed for an 18-month period from October 2004 to April 2006. RESULTS: Having excluded page visits from search engine robots, the website's homepage was visited 4452 times (mean of monthly visits: 234, range: 102-330). The web pages titled Anatomy of gastrointestinal system, Nutrition in IBD, Diagnostic tests, How to cope with IBD, and IBD in women were the most favorite in general section. The web page titled IBD treatment was the most visited in both CD and UC sections followed by the web pages on cause of disease, diagnostic procedures and complications in CD section; and those titled symptoms, cause of disease and risk factors in the UC section. Overall, the content evaluation polls received 294 hits (from 186 unique visitors) of which, 196 (67%) were from patients, 30 (10%) from patients' relatives/friends, 21 (7%) from doctors, and 47 (16%) from other groups. During the 18-month period, 47 patients registered in the self-help forum, 24 threads were opened, and 97 posts (33 in CD and 64 in UC section) were sent. CONCLUSIONS: Considering the increasing trend of Internet use in developing countries like Iran, and the consequent increase in the proportion of Internet-using patients, and finally the time constraints gastroenterologists face answering patients' questions; similar websites seem to be effective ways of patient education in close future.     

肠上皮淋巴细胞与炎症性肠病相关性的研究进展

肠上皮淋巴细胞（iIEL）定位于消化道黏膜上皮细胞间，与肠上皮细胞紧密接触并相互作用，介导黏膜局部免疫防御和维持肠黏膜组织稳定性。iIEL通过其细胞毒活性及所分泌的细胞因子调节肠上皮细胞的凋亡及再生，在炎症性肠病的发生及发展中起一定作用。     

IL-27在小鼠结肠炎中的作用及对NLRP3炎性小体的影响

目的:观察白细胞介素27(IL-27)对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠结肠组织学及NOD样受体蛋白3(NLRP3)炎性小体的影响。方法:将48只雄性C57BL/6小鼠随机分为正常对照组(自由进食饮水)、DSS模型组(饮用3%DSS溶液)、低剂量IL-27组和高剂量IL-27组(在饮用DSS溶液的基础上分别腹腔注射500ng和1μg IL-27)。12 d后行疾病活动指数(DAI)及组织损伤指数(HI)评分评估炎症程度,取结肠组织行免疫组化、Western blot及qPCR检测,取血清行ELISA检测IL-1β和IL-18水平。结果:与对照组相比,模型组的DAI评分和HI评分提示小鼠的结肠炎症明显增强(P0.05),NLRP3和IL-1β的mRNA表达水平增高,NLRP3和cleaved caspase-1的蛋白水平增高,血清中IL-1β和IL-18的含量增加;与模型组相比,高剂量IL-27组的DAI评分和HI评分提示小鼠的结肠炎症明显减轻(P0.05),NLRP3和IL-1β的mRNA表达水平下降,NLRP3和cleaved caspase-1的蛋白水平降低,血清中IL-1β中和IL-18的含量也减少;与模型组比较,低剂量IL-27组除了血清中IL-1β和IL-18含量减少外,上述各项指标的差异无统计学显著性。结论:IL-27可减轻DSS结肠炎模型小鼠的炎症程度并且可抑制NLRP3炎性小体的表达和激活。     

Isolation and preliminary probiotic selection of lactobacilli from koumiss in Inner Mongolia

From 16 samples of traditional fermented koumiss collected in Inner Mongolia Autonomous Region of China, forty‐eight lactobacilli strains were isolated and phenotypically characterized by their abilities to ferment different carbohydrates and by additional biochemical tests. The dominant lactobacilli species were identified as L. casei (17 strains), L. helveticus (10 strains) and L. plantarum (8 strains), with a lower frequency of isolation for L. coryniformis subsp. coryniformis (5 strains), L. paracasei (3 strains), L. kefiranofaciens (2 strains), L. curvatus (1 strain), L. fermentum (1 strain) and W. kandleri (1 strain). The pH values of all these samples were ranging from 3.37 to 3.94. In isolates, L. casei Zhang, L. helveticus ZL12‐1, and L. plantarum BX6‐6 were selected as potentially probiotic strains through the preliminary tests including resistance to low acid, abilities to grow in MRS with bile salts, antimicrobial activities and the viabilities during prolonged cold storage in fermented milk. Moreover 16S rDNA was conducted to confirm the identification. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

生物材料力学研究新进展

作为生物力学中一个快速发展的重要研究领域,生物材料力学旨在通过实验研究和理论分析,揭示各种天然生物材料的功能、性能、结构和组分之间的基本关系和机理,并为新材料的仿生设计等提供来自大自然的启示。本文综述了近年来我国学者在该领域取得的一些最新研究进展,主要内容包括珍珠母、牛角等生物复合材料的强韧化机制,生物材料表面浸润特性与微纳米结构之间的关系,以及相关的一些仿生应用。本文还简要介绍了本期专刊所刊登的7篇邀请文章。     

TNBS诱导炎症性肠病大鼠结肠神经元tau蛋白磷酸化以及COX-2表达的变化

目的:探讨三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)诱导炎症性肠病(inflammatory bowel disease,IBD)模型大鼠结肠神经元tau蛋白磷酸化和环氧合酶2(COX-2)表达的变化。方法:30只健康雄性成年Wistar大鼠随机分为对照组、IBD模型组和TNBS组,每组10只,IBD模型组以TNBS乙醇连续灌肠14 d造模,对照组和TNBS组分别以等量生理盐水和TNBS灌肠;观察大鼠的一般情况和结肠病理组织学改变,用anti-Hu作为神经元标志以免疫荧光法检测结肠黏膜下神经元的数量变化,免疫荧光双染色检测结肠黏膜下神经元COX-2和磷酸化tau231、tau262的表达变化。结果:与对照组比较,IBD模型组大鼠结肠黏膜下神经元数量明显减少(P0.05),神经元tau蛋白磷酸化程度明显升高(P0.05),而TNBS组大鼠神经元数量与对照组相比无显著差别;对照组和TNBS组大鼠结肠黏膜下神经元几乎不表达COX-2,IBD模型组大鼠结肠神经细胞胞核和胞浆中均有COX-2的表达,与对照组和TNBS组相比有显著差异(P0.05)。结论:TNBS乙醇诱导IBD模型大鼠结肠黏膜下神经元减少,可能与tau蛋白高度磷酸化及COX-2表达有关。     

Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice

Galectins have recently emerged as central regulators of the immune system. We have previously demonstrated that carbohydrate-dependent binding of galectin-2 induces apoptosis in activated T cells. Here, we investigate the potential therapeutic effect of galectin-2 in experimental colitis. Galectin-2 expression and its binding profile were determined by immunohistochemistry. Acute and chronic colitis was induced by dextran sodium sulfate administration and in a T-cell transfer colitis model. Apoptosis was assessed by TdT-mediated dUTP-biotin nick-end labeling, and cytokine secretion was determined by cytometric bead array. We show that galectin-2 was constitutively expressed mainly in the epithelial compartment of the mouse intestine and bind to lamina propria mononuclear cells. During colitis, galectin-2 expression was reduced, but could be restored to normal levels by immunosuppressive treatment. Galectin-2 treatment induced apoptosis of mucosal T cells and thus ameliorated acute and chronic dextran-sodium-sulfate-induced colitis and in a T-helper-cell 1-driven model of antigen-specific transfer colitis. Furthermore, the pro-inflammatory cytokine release was inhibited by galectin-2 treatment. In preliminary toxicity studies, galectin-2 was well tolerated. Our study provides evidence that galectin-2 induces apoptosis in vivo and ameliorates acute and chronic murine colitis. Furthermore, galectin-2 has no significant toxicity over a broad dose range, suggesting that it may serve as a new therapeutic agent in the treatment of inflammatory bowel disease.

Evaluation of QT and P wave dispersion and mean platelet volume among inflammatory bowel disease patients

Background: In inflammatory bowel disease (IBD) number of thromboembolic events are increased due to hypercoagulupathy and platelet activation. Increases in mean platelet volume (MPV) can lead to platelet activation, this leads to thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT-dispersion and P-wave dispersion are predictors of ventricular arrhythmias and atrial fibrilation; MPV is accepted as a risk factor for acute coronary syndromes, we aimed at evaluating the correlations of these with the duration of disease, its localization and activity.Methods: The study group consisted of 69 IBD (Ulcerative colitis n: 54, Crohn''s Disease n:15) patients and the control group included 38 healthy individuals. Disease activity was evaluated both endoscopically and clinically. Patients with existing cardiac conditions, those using QT prolonging medications and having systemic diseases, anemia and electrolyte imbalances were excluded from the study. QT-dispersion, P-wave dispersion and MPV values of both groups were compared with disease activity, its localization, duration of disease and the antibiotics used.Results: The P-wave dispersion values of the study group were significantly higher than those of the control group. Duration of the disease was not associated with QT-dispersion, and MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were similar between the active and in mild ulcerative colitis patients. QT-dispersion levels were similar between IBD patients and the control group. No difference was observed between P-wave dispersion, QT-dispersion and MPV values; with regards to disease duration, disease activity, and localization in the study group (p>0.05).Conclusions: P-wave dispersion which is accepted as a risk factor for the development of atrial fibirilation was found to be high in our IBD patients. This demonstrates us that the risk of developing atrial fibrillation may be high in patients with IBD. No significant difference was found in the QT-dispersion, and in the MPV values when compared to the control group.     

Proteomics and chronic inflammatory bowel diseases

Inflammatory bowel diseases (IBD) are relatively frequent in developed countries. Physiopathological events involved in the etiology of IBDs include activation of immune, mesenchymal and epithelial cells. This review gives an overview of the currently applied proteomics technologies. It describes metabolic changes and goes into the approaches using this methodology to understand the molecular mechanisms implicated in the development of the disease.