克罗恩病肠道纤维化的易感基因和血清标志物  

Susceptibility genes and serum markers of intestinal fibrosis in Crohn disease

作　　者：李冠炜 任建安[1] 黎介寿[1] 

机构地区：[1]南京军区南京总医院普通外科研究所,210002

出　　处：《中华胃肠外科杂志》2017年第11期1326-1330,共5页Chinese Journal of Gastrointestinal Surgery

摘　　要：克罗恩病（Crohn disease，CD）是一种病因不明的肠道慢性迁延性炎性疾病。随着病程的发展，多数CD患者可出现肠道纤维化并逐步发展为肠道的纤维化狭窄，进而导致难治性腹痛甚至肠梗阻，最终需要一次乃至多次手术治疗。目前，CD的病因和发病机制尚不清楚。研究认为，遗传、环境和免疫三者相互作用参与CD发病，并可能决定CD患者的肠道纤维化发生。近年来，国内外学者对CD遗传因素的研究发现，基因突变与CD肠道纤维化相关。多项研究表明NOD2、ATG16L1、CX3CR1、IL-23R和MMP3等基因的某些位点突变与纤维梗阻型CD存在关联性。除遗传因素之外，血清中的细胞外基质分子、生长因子、miRNAs和微生物抗体等均与CD患者发生肠道纤维化梗阻或狭窄具有相关性，但不同中心的研究结果不甚一致。因此，探索肠道纤维化的无创血清标志物具有重要的临床意义。通过高通量的蛋白质组学技术筛选出灵敏度、特异性更高的血清学指标，是一个值得深入研究的方向。通过易感基因筛查出易出现纤维梗阻表型的患者，并结合无创的血清标志物早期发现肠道纤维化，将有助改善CD的治疗效果和降低手术率。本文试对目前关于CD肠道纤维化的易感基因和血清标志物进行综述。Crohn disease （CD） is a chronic inflammatory disease which progressively affects the digestive tract with unknown etiology. During the disease course, intestinal fibrosis will gradually develop in many CD patients and results in irreversible fibrosis stricture, causing refractory abdominal pain and even intestinal obstruction, and necessitating one or more surgical interventions. Thus far the exact etiology of CD remains unknown. It is believed that genetic, environmental and immunologic factors are involved, which may also predict the development of intestinal fibrosis. Recent studies have found the association of mutations in genes, such as NOD2, ATG16L1, CX3CR1, IL-23R and MMP3 with the fibrogenic phenotype of CD. In addition, serum extracellular matrix molecules, growth factors, miRNAs and microbial antibodies have also been linked to the fibrogenesis in CD patients, however the results of researches were divergent. Therefore it is of significance to explore noninvasive markers of intestinal fibrosis with high sensitivity and specificity, and the high-throughput proteomic technique may be an approach that deserves further investigation. Screening the high-risk patients for the fibrostenotic phenotype of CD by susceptibility genes, and early detection of intestinal fibrosis using noninvasive serum markers, will help improve the treatment outcomes and reduce the surgical rates. The article aims at summarizing the current susceptibility genes and serum markers of intestinal fibrosis in CD.

关 键 词：肠道纤维化 克罗恩病 易感基因 血清标志物 

分 类 号：R574.62[医药卫生—消化系统]