IBS症状在溃疡性结肠炎缓解期中的发生情况及影响因素

目的：探讨肠易激综合征（IBs）症状在溃疡性结肠炎缓解期中的发生情况及影响因素。方法：采用问卷调查的形式对来我院就诊的124例溃疡性结肠炎（UC）患者进行调查和随访,对在缓解期的75例患者根据IBS症状的发生情况进行症状评估、心理状态评分,探讨1BS症状在缓解期溃疡性结肠炎患者中的发生情况以及影响因素。结果：溃疡性结肠炎缓解期患者IBS症状的发生率为43％,且女性缓解期溃疡性结肠炎患者出现IBS症状的比例（57％）显著高于男性患者（30％）,而症状达到IBS诊断标准的患者焦虑或者抑郁评分明显高于未达IBS诊断标准者（P〈0．000）。结论：溃疡性结肠炎缓解期患者IBS症状的发生率较高,与患者的心理及精神状态有着密切的关系。     

溃疡性结肠炎与缺血性结肠炎临床特征内镜特点相关分析

目的：提高缺血性结肠炎（IC）和与溃疡性结肠炎（UC）诊断的正确率。方法：选择2008年1月至2011年6月的住院患者,确诊IC 43例,UC 36例,对其临床特征、内镜特点进行回顾性比较分析。结果：组间性别、年龄、病程和基础疾病比较差异有统计学意义（P〈0.05）,而主要临床表现比较,差异无统计学意义。IC组以老年女性多见,病程短,多伴发心脑血管等基础疾病（29/43,67.0%）。IC组C反应蛋白高于UC组,血小板低于UC组（P〈0.05）。IC多累及乙状结肠,直肠少见;病变为区域局限性,溃疡为纵形或不规则形,病灶愈合迅速,病理以黏膜炎症为主。UC组病变多起源于直肠,一般累及肠壁全周,病变为倒灌连续性,以散在针尖样地图状溃疡为主,病理表现为隐窝炎和脓肿。结论：年龄、病程、基础疾病、C反应蛋白、内镜及病理特征是鉴别诊断的要点。     

Role of Janus Kinase 3 in Mucosal Differentiation and Predisposition to Colitis

Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase expressed in both hematopoietic and nonhematopoietic cells. Previously, we characterized the functions of Jak3 in cytoskeletal remodeling, epithelial wound healing, and mucosal homeostasis. However, the role of Jak3 in mucosal differentiation and inflammatory bowel disease was not known. In this report, we characterize the role of Jak3 in mucosal differentiation, basal colonic inflammation, and predisposition toward colitis. Using the Jak3 knock-out (KO) mouse model, we show that Jak3 is expressed in colonic mucosa of mice, and the loss of mucosal expression of Jak3 resulted in reduced expression of differentiation markers for the cells of both enterocytic and secretory lineages. Jak3 KO mice showed reduced expression of colonic villin, carbonic anhydrase, secretory mucin muc2, and increased basal colonic inflammation reflected by increased levels of pro-inflammatory cytokines IL-6 and IL-17A in colon along with increased colonic myeloperoxidase activity. The inflammations in KO mice were associated with shortening of colon length, reduced cecum length, decreased crypt heights, and increased severity toward dextran sulfate sodium-induced colitis. In differentiated human colonic epithelial cells, Jak3 redistributed to basolateral surfaces and interacted with adherens junction (AJ) protein β-catenin. Jak3 expression in these cells was essential for AJ localization of β-catenin and maintenance of epithelial barrier functions. Collectively, these results demonstrate the essential role of Jak3 in the colon where it facilitated mucosal differentiation by promoting the expression of differentiation markers and enhanced colonic barrier functions through AJ localization of β-catenin.     

VPAC1 (vasoactive intestinal peptide (VIP) receptor type 1) G protein-coupled receptor mediation of VIP enhancement of murine experimental colitis

Distinct roles of the two T cell G protein-coupled receptors for vasoactive intestinal peptide (VIP), termed VPAC1 and VPAC2, in VIP regulation of autoimmune diseases were investigated in the dextran sodium sulfate (DSS)-induced murine acute colitis model for human inflammatory bowel diseases. In mice lacking VPAC2 (VPAC2-KO), DSS-induced colitis appeared more rapidly with greater weight loss and severe histopathology than in wild-type mice. In contrast, DSS-induced colitis in VPAC1-KO mice was milder than in wild-type mice and VPAC2-KO mice. Tissues affected by colitis showed significantly higher levels of myeloperoxidase, IL-6, IL-1β and MMP-9 in VPAC2-KO mice than wild-type mice, but there were no differences for IL-17, IFN-γ, IL-4, or CCR6. Suppression of VPAC1 signals in VPAC2-KO mice by PKA inhibitors reduced the clinical and histological severity of DSS-induced colitis, as well as tissue levels of IL-6, IL-1β and MMP-9. Thus VIP enhancement of the severity of DSS-induced colitis is mediated solely by VPAC1 receptors.     

High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions

Previously, we reported that oral feeding of 1% green tea polyphenols (GTPs) aggravated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we assessed the toxicity of 1% GTPs in several organs from normal and DSS-exposed mice. Sixty-two male ICR mice were initially divided into four groups. Non-treated group (group 1, n = 15) was given standard diet and water, GTPs (group 2, n = 15) received 1% GTPs in diet and water, DSS (group 3, n = 15) received diet and 5% DSS in water, and GTPs + DSS group (group 4, n = 17) received 1% GTPs in diet and 5% DSS in water. We found that group 4 significantly increased (P < 0.05) kidney weight, the levels of serum creatinine and thiobarbituric acid-reactive substances in both kidney and liver, as compared with those in group 3. The mRNA expression levels of antioxidant enzymes and heat-shock proteins (HSPs) in group 4 were lower than those of group 3. For instance, heme oxygenase-1 (HO-1), HSP27, and 90 mRNA in the kidney of group 4 were dramatically down-regulated as compared with those of group 3. Furthermore, 1% GTPs diet decreased the expression of HO-1, NAD(P)H:quinone oxidoreductase 1 (NQO1) and HSP90 in kidney and liver of non-treated mice. Taken together, our results indicate that high-dose GTPs diet disrupts kidney functions through the reduction of antioxidant enzymes and heat-shock protein expressions in not only colitis but also non-treated ICR mice.     

复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的临床研究

目的:观察复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的疗效。方法:第一阶段将102例轻、中度溃疡性结肠炎患者随机分成A组(34例)、B组(34例)和C组(34例),分别服用美沙拉嗪片、复方嗜酸乳杆菌、美沙拉嗪+复方嗜酸乳杆菌治疗12周后观察3组临床疗效,缓解率及缓解时间。第二阶段将各组缓解者随访1年,观察3组维持时间及复发率。结果:3组临床疗效评价,临床缓解时间、缓解率比较无显著性差异见(P>0.05),3组患者维持临床缓解时间、复发率比较差异无显著性意义(P>0.05)。所以由中国株嗜酸乳杆菌,日本株嗜酸乳杆菌、粪链球菌和枯草杆菌等四种菌粉组成的复方片剂是值得推荐的维持治疗缓解期UC的有效药物;两者联合用药并未增效,联合使用复方嗜酸乳杆菌片和美拉沙嗪作为溃疡性结肠炎的联合维持治疗是没有必要的。结论:复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用的疗效与美拉沙嗪比较无差异,没有必要联合使用复方嗜酸乳杆菌片和美拉沙嗪作为溃疡性结肠炎的联合维持治疗。     

The intestinal microbiota: from health to disease,and back

Our understanding of the composition and the function of the intestinal microbiota has significantly increased over the past few years. In a series of reviews focusing on the role of the intestinal microbiota in health and disease, we explore recent conceptual and technological advances in this rapidly evolving research arena.     

五味子甲素对溃疡性结肠炎小鼠血液流变性及凝血功能的影响

目的:考察五味子甲素对溃疡性结肠炎(ulcerative colitis,UC)小鼠血液流变性及凝血功能的影响。方法:以三硝基苯磺酸(TNBS)灌肠制备溃疡性结肠炎小鼠模型,UC小鼠随机分为模型组、阳性对照组及五味子甲素高、中、低剂量组(80,40,20mg/kg),同时设立正常对照组,每组10只。灌胃给药,正常组、模型组分别给予等体积蒸馏水,阳性对照组给予500 mg/kg柳氮磺吡啶(SASP),连续给药14 d。观察五味子甲素对UC小鼠全血黏度及凝血功能的影响。结果:与UC模型组小鼠比较,五味子甲素可显著降低UC小鼠全血黏度(P0.05),延长出血时间(bleeding time,BT)(P0.01)及凝血时间(clotting time,CT)(P0.05),其中甲素高剂量组作用最强,与SASP阳性对照组相当,并呈剂量依赖性。结论:五味子甲素可改善UC小鼠血液流变性及凝血功能,此作用有利于UC溃疡黏膜的修复与疾病的治疗。     

Amelioration of dextran sulfate sodium-induced colitis in mice by oral administration of beta-caryophyllene, a sesquiterpene

beta-Caryophyllene (BCP), a naturally occurring plant sesquiterpene, was examined for anti-inflammatory activity in a mouse model of experimental colitis induced by dextran sulfate sodium (DSS). Colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7 days. BCP in doses of 30 and 300 mg/kg was administered orally once a day, beginning concurrently with exposure to DSS. The body weight and colon length were measured, and histological damage and myeloperoxidase (MPO) activity as well as inflammatory cytokines were assessed in both serum and colonic tissue after 7 days of treatment with DSS. The DSS treatment damaged the colonic tissue, increased MPO activity and inflammatory cytokines, lowered the body weight, and shortened the length of the colon. Oral administration of BCP at 300 mg/kg significantly suppressed the shortening of colon length and slightly offset the loss of body weight. BCP treatment (300 mg/kg) also significantly reduced the inflammation of colon and reversed the increase in MPO activity that had been induced by exposure to DSS. Further, BCP significantly suppressed the serum level of IL-6 protein (a 55% reduction) as well as the level of IL-6 mRNA in the tissue. These results demonstrate that BCP ameliorates DSS-induced experimental colitis, and may be useful in the prevention and treatment of colitis.     

A Gut Microbial Metabolite of Linoleic Acid, 10-Hydroxy-cis-12-octadecenoic Acid,Ameliorates Intestinal Epithelial Barrier Impairment Partially via GPR40-MEK-ERK Pathway

Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because of their various physiological properties. Dysfunction of tight junction (TJ) in the intestine contributes to the pathogenesis of many disorders such as inflammatory bowel disease. We evaluated the effects of five novel gut microbial metabolites on tumor necrosis factor (TNF)-α-induced barrier impairment in Caco-2 cells and dextran sulfate sodium-induced colitis in mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF-α and dextran sulfate sodium-induced changes in the expression of TJ-related molecules, occludin, zonula occludens-1, and myosin light chain kinase. HYA also suppressed the expression of TNF receptor 2 (TNFR2) mRNA and protein expression in Caco-2 cells and colonic tissue. In addition, HYA suppressed the protein expression of TNFR2 in murine intestinal epithelial cells. Furthermore, HYA significantly up-regulated G protein-coupled receptor (GPR) 40 expression in Caco-2 cells. It also induced [Ca²⁺]_i responses in HEK293 cells expressing human GPR40 with higher sensitivity than linoleic acid, its metabolic precursor. The barrier-recovering effects of HYA were abrogated by a GPR40 antagonist and MEK inhibitor in Caco-2 cells. Conversely, 10-hydroxyoctadacanoic acid, which is a gut microbial metabolite of oleic acid and lacks a carbon-carbon double bond at Δ12 position, did not show these TJ-restoring activities and down-regulated GPR40 expression. Therefore, HYA modulates TNFR2 expression, at least partially, via the GPR40-MEK-ERK pathway and may be useful in the treatment of TJ-related disorders such as inflammatory bowel disease.