溃疡性结肠炎的治疗进展

溃疡性结肠炎是难治性疾病,传统的治疗药物包括氨基水杨酸类、激素、免疫抑制剂等,近来生物治疗、营养治疗、白细胞去除术等成为研究热点。溃疡性结肠炎的治疗应该采用个体化、标准治疗与辅助治疗相结合的综合治疗。     

热瘀散对胃肠湿热型溃疡性结肠炎大鼠血清IL-8、IL-10的影响

目的：探讨热瘀散治疗胃肠湿热型溃疡性结肠炎（ulcerative colitis,UC）的作用机制。方法：雄性Wistar大鼠50只,随机分为正常对照组、模型组、柳氮磺胺吡啶（salicylazosulfapyridine,SASP）组、热瘀散低剂量组、热瘀散高剂量组。采用复合因素（高脂、高糖饮食加湿热环境）复制胃肠湿热证模型,再用2,4,6-三硝基苯磺酸（trinitro—benzene—sulfonic acid,TNBS）与500ml／L乙醇复合溶液复制溃疡性结肠炎模型。模型复制后各组大鼠给予相应药物治疗,连续15d,第16天处死动物,观察大鼠结肠组织病理变化,检测血清白介素（interleukin,IL）-8和IL-10的含量。结果：模型组大鼠结肠组织大体评分、病理组织学变化表明模型复制成功,热瘀散明显改善结肠组织的病理损伤,热瘀散高、低剂量及SASP均可降低血清IL-8水平,提高血清IL-10水平。结论：热瘀散通过抑制促炎细胞因子,促进抗炎细胞因子生成,发挥对UC的治疗作用。     

溃疡性结肠炎伴不全肠梗阻并严重感染的诊治分析

【目的】探讨溃疡性结肠炎(UC)伴不全肠梗阻并发严重感染的诊治方法。【方法】回顾性分析本院近期收治的一例 UC 伴不全肠梗阻并发严重感染患者的临床资料,三次入住本院消化内科症状无明显改善后转入本科室治疗,拟逐步停用激素及免疫抑制剂后行探查手术,同时予以肠内外营养支持治疗,三个月后行腹腔镜结肠肝曲癌根治+左半结肠切除术。【结果】患者腹泻症状较术前明显缓解,未再诉腹痛、腹胀;体温恢复正常;肛瘘病情好转;术后病检结果为 UC 伴结肠肝曲癌变。【结论】UC 患者在使用激素、抗免疫治疗时出现不全肠梗阻应早期预防性给予抗感染治疗,避免出现爆发感染,疗效不佳时应尽早手术治疗;对于病程长的 UC 患者出现类似克隆恩病肠壁增厚不全肠梗阻时应早期手术,谨防癌变。     

Ischemic colitis in rats

Left-sided ischemic colitis was induced in 44 inbred Male Fischer rats of the same age by a standardized devascularization procedure. Fifteen animals had nothing else done (Group I). Twentynine animals had feces evacuated from the left colon and received an enema just before the procedure; 14 had a sterile-water enema (Group II), and 15 had a 1 per cent hydrocortisone enema (Group III). At sacrifice, 72 hours after the surgical procedure, the mucosal surface grossly involved in ischemic changes was measured. The mean area of ischemic changes in Group I was significantly greater than that of either Group II or Group III (P<.05). The incidence of circumferential changes was highest in Group I and lowest in Group III; the difference between Group I and Group III was marginally significant (P=.06). Read at the meeting of the American Society of Colon and Rectal Surgeons, Colorado Springs, Colorado, June 7 to 11, 1981. Supported by the Veterans Administration.     

Galacto-oligosaccharides Stimulate the Growth of Bifidobacteria but Fail to Attenuate Inflammation in Experimental Colitis in Rats

Background: Galacto-oligosaccharides potentially attenuate colonic inflammation by two mechanisms: through beneficial effects on intestinal microflora and by increasing the colonic short-chain fatty acid concentration. The purpose of this study was to investigate the effects of galacto-oligosaccharides on the development of inflammation and on the growth of bifidobacteria in trinitrobenzene sulphonic acid (TNBS)-induced colitis, a model that has been shown to benefit from short-chain fatty acid administration and to be associated with alterations in the colonic microflora. Methods: Rats were given daily either whey-derived or lactose-derived galacto-oligosaccharides (4 g kg -1 day -1 , p.o.), starting 10 days before colitis induction, or dexamethasone (2 mg kg -1 day -1 , s.c., a positive control), starting at colitis induction. Colon wet weight, macroscopic damage and myeloperoxidase activity were assessed 72 h after the induction of colitis. Faecal bifidobacteria were counted at the beginning of the study, and immediately before and 72 h after colitis induction. Results: Galacto-oligosaccharides increased the colonic levels of bifidobacteria but also the levels of other bacterial species. Neither whey-derived nor lactose-derived galacto-oligosaccharides reduced the severity of inflammation. Conclusions: Galacto-oligosaccharides are able to modify gut microflora in severe TNBS-induced colitis, but unable to attenuate the inflammation.     

大蒜素对三硝基苯磺酸诱导大鼠结肠炎的保护作用及其机制研究

背景：溃疡性结肠炎（UC）是一种病因未明的结直肠炎症,大蒜素对其防治的作用目前尚未有结论。目的：探讨大蒜素对TNBS诱导的大鼠结肠炎的保护作用及其机制。方法：80只大鼠随机分为对照组、TNBS组、大蒜素预防组、大蒜素灌胃组、大蒜素灌肠组、地塞米松组、柳氮磺吡啶组、巴柳氮钠组。以含150mg／kgTNBS的50％乙醇溶液灌肠制备大鼠结肠炎模型。造模2周后处死大鼠。行大体评分和病理学评分,以ELISA法测定血清TNF-α、IL-1β、IL-10、IL4含量,蛋白质印迹法检测NF—κB表达。结果：与对照组相比,TNBS组大体和病理学评分均明显升高（P〈0．05）,体质量明显降低（P〈0．05）,血清TNF-α、IL-1B含量显著升高（P〈0．05）,血清IL-4、IL-10含量显著降低（P〈0．05）,NF-κB表达明显升高（P〈0．05）;给予大蒜素预防或治疗后,上述指标均明显改善（P〈0．05）,但疗效低于地塞米松组、柳氮磺吡啶组、巴柳氮钠组。结论：大蒜素对TNBS诱导的大鼠结肠炎有保护作用,可能是通过调控细胞因子和NF—κB而发挥作用的。     

C反应蛋白对溃疡性结肠炎患者活动性的评价

目的 评估C反应蛋白(CRP)对溃疡性结肠炎患者不同病情程度的临床价值.方法 分析40例活动期和34例缓解期溃疡性结肠炎患者血清CRP、和血小板平均体积的水平及关系,比较临床病情程度对CRP的影响.结果 活动期溃疡性结肠炎患者血清CRP浓度明显高于缓解期患者,两组差别有统计学意义(P＜0.05),重型溃疡性结肠炎患者血清CRP浓度显著高于中型溃疡性结肠炎患者(P＜0.05);中型溃疡性结肠炎患者血清CRP浓度亦明显高于轻型溃疡性结肠炎患者(P＜0.05).结论 CRP水平升高能反映活动期溃疡性结肠炎患者临床病情严重程度,为临床诊治提供重要理论依据.     

Hematopoietic plakophilin‐3 regulates acute tissue‐specific and systemic inflammation in mice

Plakophilin‐3 (PKP3) is a member of the armadillo protein family, which is important in cell?cell contacts and signaling during development and tumorigenesis. In conventional facilities, PKP3‐deficient mice (PKP3^?/?) develop spontaneous dermatitis, indicating a possible involvement of PKP3 in inflammatory responses. Here, we show that PKP3 deficiency sensitizes mice to irritant contact dermatitis induced by phorbol myristate acetate (PMA). This sensitization occurred in mice with PKP3 deficiency in the hematopoietic system (PKP3^?/?hem), but not if the deficiency was specific to skin keratinocytes (PKP3^?/?ker). In a model of dextran sulfate sodium induced colitis, ubiquitous PKP3 deletion, but not intestinal epithelial PKP3 deficiency (PKP3^?/?IEC), impaired survival from disease. Interestingly, PKP3^?/?hem mice also displayed increased sensitivity to dextran sulfate sodium induced colitis. Finally, PKP3^?/? mice were more sensitive to the lethality of lipopolysaccharide (LPS) injection than wild‐type (WT) mice, and this phenotype was associated with increased intestinal permeability. PKP3^?/?IEC mice did not reproduce the enhanced endotoxin reactivity of PKP3^?/? mice, in contrast to PKP3^?/?hem mice. Finally, in vitro stimulation of WT neutrophils with LPS or PMA increased Pkp3 expression. In conclusion, our data highlight a novel role for hematopoietic PKP3 in the regulation of both locally and systemically induced immune responses. Nonetheless, further research is needed to unravel the underlying mechanism.     

Arginase activity in alternatively activated macrophages protects PI3Kp110δ deficient mice from dextran sodium sulfate induced intestinal inflammation

Alternatively activated or M2 macrophages have been reported to protect mice from intestinal inflammation, but the mechanism of protection has not been elucidated. In this study, we demonstrate that mice deficient in the p110δ catalytic subunit activity of class I phosphatidylinositol 3‐kinase (PI3Kp110δ) have increased clinical disease activity and histological damage during dextran sodium sulfate (DSS) induced colitis. Increased disease severity in PI3Kp110δ‐deficient mice is dependent on professional phagocytes and correlates with reduced numbers of arginase I⁺ M2 macrophages in the colon and increased production of inflammatory nitric oxide. We further demonstrate that PI3Kp110δ‐deficient macrophages are defective in their ability to induce arginase I when skewed to an M2 phenotype with IL‐4. Importantly, adoptive transfer of IL‐4‐treated macrophages derived from WT mice, but not those from PI3Kp110δ‐deficient mice, protects mice during DSS‐induced colitis. Moreover, M2 macrophages mediated protection is lost when mice are cotreated with inhibitors that block arginase activity or during adoptive transfer of arginase I deficient M2 macrophages. Taken together, our data demonstrate that arginase I activity is required for M2 macrophages mediated protection during DSS‐induced colitis in PI3Kp110δ‐deficient mice.