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溃疡性结肠炎的研究进展,Introduction,IBD是一种病因尚不十分清楚的慢性非特异性肠道炎症,包括UC和CD 。 其发病率呈逐年上升趋势,且多为青壮年发病,临床表现复杂,并发症严重,肠外表现多样,严重影响个人生活质量和社会生产力。 此外,因其有癌变的风险,备受广大医生的重视。 近年来在国内外IBD基础与临床研究高潮迭起,基础研究的成果直接指向临床治疗,取得了划时代的进展。 探讨和摸索适合国人的治疗方案以降低重症UC的并发症和死亡率显得十分重要。,Epidemiolgy,The incidence of UC ranged from 1.0 to 2.0 per 100 000 person years. The prevalence of UC has ranged from 4.0 to 44.3 per 100 000. In a recent study, the speculated prevalence was 11.6/100 000 in China. Compared to time trends in the West, there appears to be a time lag phenomenon involving incidence and and prevalence of IBD with regard to the Asian experience. Ouyang Q, Tandon R, Goh KL et al. Management consensus of inflammatory bowel disease for the Asia-Pacific region. J Gastroenterol. Hepatol. 2006; 21: 177282. Lennrd-Jones JE. Incidence of infammatory bowel disease across Europe:is there a difference between north and south?. Gut 1996; 39: 690-697.,Etiology and Pathogenesis,目前对IBD病因和发病机制的认识可概括为: 环境因素作用于遗传易感者,在肠道菌群丛的参与下,启动了肠道免疫系统及非免疫系统,最终导致免疫反应和炎症过程。 可能是由于抗原的持续刺激或(及)免疫调节紊乱,这种免疫炎症反应表现为过度亢进或难于自限。 Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet 2007;369:16271640. Brown SJ,Mayer IThe immune response in inflammatory bowel diseaseAm J Gastroenterol,2007,102:20582069 Bernstein CN,Shanahan FDisorders of a modern lifestylel reconciling the epidemiology of inflammatory bowel diseasesGut,2008,57:1185-1191,Family history,Kitahora et al. found a strong familial occurrence in UC among Japanese patients. In a Korean study, a similar familial aggregation was also reported. Kitahora T, Utsunomiya T, Yokota A. Epidemiological study of ulcerative colitis in Japan: incidence and familial occurrence. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan. J. Gastroenterol. 1995; 30 (Suppl. 8): 58. Park ER, Yang SK, Myung SJ et al. Familial occurrence of ulcerative colitis in Korea. Korean J. Gastroenterol. 2000; 36: 7704.,Risk factors,Objective To screen the risk factors of inflammatory bowel disease(IBD)by case investigation Methords 72 determined IBD patients and 72 paired healthy subjects were surveyed with an organized inventory comprising of relevant items to IBDCOX regression method was used to screen the statistically significant risk factors for IBD Results COX regression indicated the statistical significance in stressmilk and fried food over the other postulated risk factorsfor IBD Conclusion Stress,milk and fried food are the potential risk factors for IBD Kaichun Wu et al. Investigation on the risk factors of inflammatory bowel disease:A paired study of 72 cases. Chin J Gastroenterol Hepatol. 2006, 15(2): 161-162,Protective factors,A study from Japan found a protective effect of smoking for UC. Nam et al. found that appendectomy was protective against UC in their group of Korean patients. A case-control study of ulcerative colitis in relation to dietary and other factors in Japan. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan. J Gastroenterol. 1995; 30 (Suppl. 8): 912. Nam SW, Yang SK, Jung HY et al. Appendectomy and the risk of developing ulcerative colitis: results after control of smoking factor. Korean J. Gastroenterol. 1998; 32: 5560. Vleggaar FP, Lutgens MW, Claessen MM. Review article: the relevance of surveillance endoscopy in long-lasting inflammatory bowel disease. Aliment. Pharmacol. Ther. 2007; 26 (Suppl. 2): 4752.,Serological markers,The two most widely studied serological markers in inflammatory bowel disease in recent years have been p-ANCA and ASCA. The clinical utility of p-ANCA or ASCA testing in the diagnosis of inflammatory bowel disease, in patients with non-specific gastrointestinal symptoms, is limited because of the varying seroprevalence of these antibodies in patients with inflammatory bowel disease and the inadequate sensitivity of the assays. Lawrance IC, Murray K, Hall A, Sung JJ, Leong R. A prospective comparative study of ASCA and pANCA in Chinese and Caucasian IBD patients. Am. J. Gastroenterol. 2004; 99: 218694 Reese GE, Constantinides VA, Simillis C et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006 (Oct); 101 (10): 241022. Bossuyt XSerologic markers in inflammatofy bowel diseaseC1in Chem 2006:52:171一181,Serum proteins,目的 应用蛋白质组学寻找溃疡性结肠炎(UC)血清差异蛋白,初步探索UC可能的生物标志物。 方法 收集UC患者30例和健康对照者30名的血清标本,双向凝胶电泳(2-DE)分离等量混合血清的蛋白质,运用图像分析软件进行比较和分析,识别差异表达蛋白质。应用基质辅助激光解吸电离飞行时间质谱(MAI,DI-TOF-MS)鉴定部分差异蛋白质点。 结果 UC组和对照组之间年龄、体重指数、吸烟情况和饮滔量的差异均无统计学意义(P值均o05)。初步筛选出UC患者与健康对照者存在明显差异的39个蛋白点,选择其中9个点。经质谱分析发现触珠蛋白,热休克转录因子2,受体酪氨酸激酶、醛脱氢酶、载脂蛋白c一、中心粒旁物质l在UC患者中表达水平升高,角蛋白1,细丝蛋白A结合蛋白1、肌球蛋白3在UC患者中表达水平降低。 结论 采用蛋白质组学2-DE和质谱技术,筛选并鉴定出与UC相关的9个血清蛋白质,为提供新的UC生物学行为研究分子标志物奠定基础。 缪应雷,等. 溃疡性结肠炎血清差异蛋白的筛选研究. 中华消化杂志. 2010 , 30 (12): 898-901.,菌群失调,IBD患者肠遭细菌存在菌群失调,正常细菌数量减少,而致病菌、条件致病菌数量明显增多。 Duchmann等 发现。正常人对其体内肠道菌群及抗原物质耐受,而IBD患者肠黏膜免疫细胞对
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