炎症性肠病患者的自主神经功能研究

目的:探讨炎症性肠病患者的自主神经功能状态。方法:选取炎症性肠病(IBD)患者60例作为观察组,包括活动期溃疡性结肠炎(UC)37例,活动期克罗恩病(CD)23例,同期健康体检者50例作为对照组。交感神经功能采用握力试验以及卧立位血压差的方式进行检查;迷走神经功能则采用卧立位心率变化和Valsalva动作反应指数检查方法。结果:(1)观察组卧立位心率变化均值明显低于对照组,其中溃疡性结肠炎和克罗恩病心率变化均值均明显低于对照组,差异有统计学意义(P0.05);溃疡性结肠炎与克罗恩病心率变化均值差异无统计学意义(P0.05);溃疡性结肠炎和克罗恩病Valsalva动作反应指数与对照组相比差异无统计学意义(F=1.06,P0.05)。(2)观察组卧立位血压差均值明显高于对照组,握力试验的血压反应均值明显低于对照组,溃疡性结肠炎和克罗恩病卧立位血压差均值均明显低于对照组,握力试验的血压反应均值均明显低于对照组差异有统计学意义(P0.05);而溃疡性结肠炎和克罗恩病卧立位血压差均值及血压反应均值比较均无统计学差异。结论:炎症性肠病患者存在自主神经功能紊乱,交感神经功能增强而迷走神经功能相对减弱。     

白介素23 及Th17 细胞在炎症性肠病的作用

炎症性肠病(Inflammatory Bowel Diseases,IBD),是一组病因未明的累及胃肠道的慢性炎症性疾病,一般指克罗恩病(Crohn’sdisease,CD)和溃疡性结肠炎(ulcerative colitis,UC)。目前认为它是由多种因素相互作用所致的一种自身免疫性疾病,主要包括免疫、环境以及遗传等因素,其中免疫在IBD的发生过程中起着极其重要的作用。以往研究认为与T辅助细胞(T Helper cells)Th1或Th2细胞反应的增强或减弱有关。然而最近研究发现一类新细胞亚群,称为Th17细胞,与之相关的细胞因子可导致包括肠道在内的多脏器病变。Th17细胞分化过程中又需要IL-23的参与,因此IL-23/Th17细胞在炎症性肠病患者肠道内过度表达可以解释肠组织损伤的新途径,并为制定新的治疗策略提出依据。本文就IL-23/Th17轴在炎症性肠病中的作用的研究进展作一综述。     

益生菌在炎症性肠病中的治疗作用

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)。随着对肠道微生物群在IBD发病机制中作用的认识不断深入,近年来益生菌广泛应用于IBD治疗。大量临床试验结果表明,益生菌治疗IBD的疗效主要体现在对UC和贮袋炎的治疗,对CD的疗效不明确。益生菌治疗IBD可能通过促进肠道微生物群平衡、改善肠道屏障功能、调节肠道黏膜免疫及营养物质代谢等途径。     

潘氏细胞与炎症性肠病研究进展

<正>潘氏细胞(paneth cells,PCs)是小肠腺的特征性细胞,可分泌防御素等多种抗菌物质,抑制肠道细菌过度繁殖,在维持肠道内稳态、参与固有免疫方面发挥重要作用。炎症性肠病(inflammatory bowel disease,IBD)主要包括克罗恩病(crohn's disease,CD)和溃疡性结肠炎(ulcerative colitis,UC),其发病机制复杂,受环境因素、遗传因素及肠道菌群等多种因素的影响,主要表现为肠道免疫系统对肠道菌群的不良免疫反应。近年来,有关PCs与IBD的相关性研究较多,现本文就其研究进展作一综述如下。     

细胞因子在炎症性肠病中的作用

炎症性肠病(inflammatory bowel disease,IBD)是一组病因未明的以慢性胃肠道炎症为特征的疾病,包括克罗恩病(Crohn's disease,CD)和溃疡性结肠炎(ulcerative colitis,UC)。细胞因子在IBD肠道炎症反应和黏膜免疫反应中起重要作用,目前已成为研究IBD发病机制的热点,本文就其在IBD中的作用作一综述。     

白细胞介素23受体、白细胞介素17A在炎症性肠病患者中的表达及临床意义

目的：通过检测白细胞介素23受体（1L-23R）及白细胞介素17A（IL-17A）在炎症性肠病（IBD）患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义。方法：收集32例克罗恩病（CD）患者、29例溃疡性结肠炎（UC）患者及27例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-23R、IL-17AmRNA的表达情况,免疫组化技术分析IL-23R、IL-17A在肠黏膜中的原位表达。结果：与健康对照组相比,CD及UC患者肠黏膜组织内IL-23RmRNA表达显著增高（P〈0．05）,CD及UC组间的表达量差异无统计学意义（P〉0．05）。CD及UC患者肠黏膜组织内IL-17AmRNA表达显著增高（P〈0．05）,CD组肠黏膜组织内IL．17AmRNA表达显著高于uc组（P〈0．05）。免疫组化分析显示IL-23R阳性细胞在CD与uc肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-23R蛋白表达量最著增高（P〈0．05）,UC及CD组间的表达量差异无统计学意义（P〉0．05）。IL-17A阳性细胞在CD与UC肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-17A蛋白表达量最著增高（P〈0．05）。结论：IL．23R及IL-17A在IBD患者肠黏膜中表达显著增高,提示IL-23R及IL-17A表达异常与IBD的发生发展密切相关,有可能成为IBD治疗的新靶点。     

白细胞介素23受体、白细胞介素17A在炎症性肠病患者中的表达 及临床意义

目的:通过检测白细胞介素23受体(IL-23R)及白细胞介素17A(IL-17A)在炎症性肠病(IBD)患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义。方法:收集32例克罗恩病(CD)患者、29例溃疡性结肠炎(UC)患者及27例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-23R、IL-17AmRNA的表达情况,免疫组化技术分析IL-23R、IL-17A在肠黏膜中的原位表达。结果:与健康对照组相比,CD及UC患者肠黏膜组织内IL-23R mRNA表达显著增高(P<0.05),CD及UC组间的表达量差异无统计学意义(P>0.05)。CD及UC患者肠黏膜组织内IL-17A mRNA表达显著增高(P<0.05),CD组肠黏膜组织内IL-17AmRNA表达显著高于UC组(P<0.05)。免疫组化分析显示IL-23R阳性细胞在CD与UC肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-23R蛋白表达量最著增高(P<0.05),UC及CD组间的表达量差异无统计学意义(P>0.05)。IL-17A阳性细胞在CD与UC肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-17A蛋白表达量最著增高(P<0.05)。结论:IL-23R及IL-17A在IBD患者肠黏膜中表达显著增高,提示IL-23R及IL-17A表达异常与IBD的发生发展密切相关,有可能成为IBD治疗的新靶点。     

幽门螺杆菌感染对DSS结肠炎小鼠 Th17/Treg细胞亚群的影响

目的 探讨幽门螺杆菌(H.pylori)感染对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的影响。 方法 80只雌性BALB/c小鼠随机分为空白对照组(CON组,n=20)和实验组(n=60),实验组制作DSS诱导UC模型,然后分组建立成为结肠炎组(CLi组)、H.pylori持续感染的结肠炎组(Hp组)和H.pylori根除的结肠炎组(Hp Era组),每组20小鼠。实验过程中观察小鼠一般情况和疾病活动指数(DAI);在第25天、45天时处死动物,分离外周血和结肠组织中单个核细胞,流式细胞仪检测其Th17/Treg细胞亚群变化。 结果 CLi组、Hp组、Hp Era组小鼠DAI评分显著高于CON组(均P结论 H.pylori感染使DSS结肠炎小鼠UC的Th17亚群比例降低、Foxp3+Treg细胞比例增加,这种变化似乎对DSS诱导的结肠炎具有保护作用。     

益生菌对炎症性肠病幼鼠Th17细胞的调节作用

目的 观察鼠李糖乳杆菌（LGG）对炎症性肠病（IBD）幼鼠结肠白细胞介素-17A（IL-17A）水平的影响,探讨益生菌对Th17细胞的调节作用。方法 36只健康雄性SD幼鼠随机分4组：空白对照组、LGG对照组各8只,IBD组、IBD-LGG组各10只。利用2,4,6-三硝基苯磺酸（TNBS）诱导幼鼠IBD模型,观察一般状况、IBD疾病活动指数评分。第8天处死所有幼鼠,留取结肠标本,观察病理改变并采用免疫组织化学法测定结肠组织IL-17A的表达。结果 相比两对照组,IBD组、IBD-LGG组幼鼠一般状态差,IBD-LGG组便性状及隐血较IBD组缓解;IBD组、IBD-LGG组幼鼠结肠组织均见炎症改变,但IBD-LGG组较轻。IBD-LGG组DAI评分、IL-17A水平均低于IBD组,差异有统计学意义（P＜0.05）。结论 益生菌可减轻IBD幼鼠肠道炎症,其机制可能与益生菌调节Th17细胞进而调控IL-17A表达有关。     

炎症性肠病患者的肠道菌群分布与血清TNF-α与IL-6水平的相关性

目的:探讨炎症性肠病患者的肠道菌群分布与血清肿瘤坏死因子-α(TNF-α)与白介素-6(IL-6)水平的相关性。方法:选择我院收治的172例炎症性肠病患者作为观察组,同期选择在我院经询问病史及体格检查无消化道疾病的172例患者作为对照组,检测两组肠道菌群的分布与血清TNF-α与IL-6水平,并分析炎症性肠病患者肠道菌群分布与血清TNF-α与IL-6水平的相关性。结果:观察组的肠球菌、粪肠球菌和大肠埃希杆菌含量明显高于对照组,而双歧杆菌含量明显低于对照组(P0.05)。观察组的血清TNF-α与IL-6值分别为0.98±0.54 ng/m L和0.98±0.38 pg/m L,都明显高于对照组的0.61±0.37 ng/m L和0.55±0.34 pg/m L(P0.05)。观察组的双歧杆菌含量与TNF-α与IL-6呈现明显负相关性(P0.05),而肠球菌、粪肠球菌、大肠埃希杆菌含量与TNF-α与IL-6都呈现明显正相关性(P0.05)。结论:炎症性肠病患者存在益生菌含量减少、有害菌含量增加的现象,这可能与患者血清促炎因子过量表达有关,二者的共同作用可促进炎症性肠病的发生及进展。     

Chemokine and cytokine levels in inflammatory bowel disease patients

Crohn’s disease (CD) and ulcerative colitis (UC), two forms of inflammatory bowel disease (IBD), are chronic, relapsing, and tissue destructive lesions that are accompanied by the uncontrolled activation of effector immune cells in the mucosa. Recent estimates indicate that there are 1.3 million annual cases of IBD in the United States, 50% of which consists of CD and 50% of UC. Chemokines and cytokines play a pivotal role in the regulation of mucosal inflammation by promoting leukocyte migration to sites of inflammation ultimately leading to tissue damage and destruction. In recent years, experimental studies in rodents have led to a better understanding of the role played by these inflammatory mediators in the development and progression of colitis. However, the clinical literature on IBD remains limited. Therefore, the aim of this study was to evaluate systemic concentrations of key chemokines and cytokines in forty-two IBD patients with a range of disease activity compared to levels found in ten healthy donors. We found a significant increase in an array of chemokines including macrophage migration factor (MIF), CCL25, CCL23, CXCL5, CXCL13, CXCL10, CXCL11, MCP1, and CCL21 in IBD patients as compared to normal healthy donors (P < 0.05). Further, we also report increases in the inflammatory cytokines IL-16, IFN-γ, IL-1β and TNF-α in IBD patients when compared to healthy donors (P < 0.05). These data clearly indicate an increase in circulating levels of specific chemokines and cytokines that are known to modulate systemic level through immune cells results in affecting local intestinal inflammation and tissue damage in IBD patients. Blockade of these inflammatory mediators should be explored as a mechanism to alleviate or even reverse symptoms of IBD.     

Small-molecule agents for the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, debilitating condition with a significant impact on quality of life. In spite of recent advances with antibody therapies, there remains a significant unmet medical need in IBD. Ongoing research and development efforts aim to identify new therapies that will increase remission rates beyond those achieved with current standard-of-care, while maintaining a high safety margin. This review will provide an overview of the small-molecule agents that are being explored in this regard.     

益生菌在炎症性肠病治疗中的研究进展

益生菌（Probiotics）是一类能够促进肠道微生物菌群平衡,对宿主健康或生理功能产生有益作用的活性微生物。目前广泛应用于生命健康领域、科学研究、生物工程、工农业以及食品安全。大量国内外研究表明益生菌在降血压、降血糖、降血脂、抗过敏、抗炎、调节免疫、维持肠道菌群平衡等方面具有积极作用。炎症性肠病的病因和发病机制尚未完全明确,现多认为与遗传、环境、感染、免疫以及肠道微生物多因素相互作用有关。益生菌通过多种机制介导,在临床治疗炎症性肠病中扮演着重要角色。     

Purine,kynurenine, neopterin and lipid peroxidation levels in inflammatory bowel disease

The kynurenine metabolites of tryptophan may be involved in the regulation of neuronal activity and thus gut motility and secretion. We have now performed a pilot study to measure serum concentrations of purines and kynurenines in patients with mild inflammatory bowel disease, as well as in sex- and age-matched control subjects. For some analyses, the patients were subdivided into subgroups of those with Crohn's disease and those with ulcerative colitis. The analyses indicated an increased activity in one branch of the kynurenine pathway. While there was no demonstrable difference in neopterin levels in either of the patient groups compared with controls, indicating that the disorders were in an inactive quiescent phase, both groups showed significantly higher levels of lipid peroxidation products. This suggests the presence of increased oxidative stress even during relative disease inactivity. The increased level of kynurenic acid may represent either a compensatory response to elevated activation of enteric neurones or a primary abnormality which induces a compensatory increase in gut activity. In either case, the data may indicate a role for kynurenine modulation of glutamate receptors in the symptoms of inflammatory bowel disease.     

Relationship between the tumor necrosis factor alpha polymorphism and the serum C-reactive protein levels in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, including ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study was to determine the prevalence of the tumor necrosis factor alpha (TNF-) promoter polymorphisms at positions –238 and –308, and to measure the serum CRP levels in CD and UC patients and in a healthy population. The TNF- gene polymorphisms were determined by the PCR-RFLP method. Samples of 74 CD and 50 UC patients and 138 healthy Hungarian volunteers were examined. The GA substitution at position –308 (designated the TNF2 allele) was significantly less frequent among IBD patients than in the control group (P=0.0009); 15% of the CD patients and 18% of the UC patients carried the mentioned allele, which was significantly less frequent compared with the healthy population (33%, P=0.0035 and P=0.036, respectively). No difference in the GA substitution at position –238 was observed. We found the median CRP levels to be significantly higher in the active phase of the disease than in the inactive phase among the –308A allele carriers (P=0.002), while this difference was not significant when the CRP levels in the active and inactive phases were compared among the –308GG homozygous patients (P=0.084). The decreased frequency of the TNF2 allele (known to be associated with elevated TNF- production) in IBD may determine the severity of IBD through its interaction with plasma CRP levels, and may modify the pathogenesis of this chronic inflammatory disease.     

Inflammatory bowel disease: Therapeutic limitations and prospective of the stem cell therapy

Inflammatory bowel disease(IBD), consisting primarily of ulcerative colitis and Crohn's disease, is a group of debilitating auto-immune disorders, which also increases the risk of colitis-associated cancer. However, due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs(e.g., approximately 30% non-responders to anti-TNFα agents), and related serious side effects, about half of all IBD patients(in millions) turn to alternative treatment options. In this regard, mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis. However, despite the increasing clinical realization of the significance of the concept of mucosal healing, its regulation and means of therapeutic targeting remain largely unclear. Here, stemcell therapy, which uses hematopoietic stem cells or mesenchymal stem cells, remains a promising option. Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells. The overreaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process. Moreover, by differentiating into the mature intestinal epithelial cells, the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction, the root cause of the IBD. In this article, we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient's quality of life.