Manuc Teodora-Ecaterina M, Manuc Mircea M, Diculescu Mircea M
Fundeni Clinical Institute, Bucharest, Romania.
University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
Clin Exp Gastroenterol. 2016 Mar 15;9:59-70. doi: 10.2147/CEG.S53381. eCollection 2016.
Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn's disease (CD) is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient. Genome-wide association studies in patients with CD worldwide revealed several genetic mutations that increase the risk of IBD and that predispose to a more severe course of disease. Gut microbiota is considered a compulsory and an essential part in the pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different bacterial strains can be found in all patients with IBD. The discovery of Escherichia coli entero-invasive on resection pieces in patients with CD now increases the likelihood of antimicrobial or vaccine-type treatments. Recent studies targeting intestinal immunology and its molecular activation pathways provide new possibilities for therapeutics. In addition to antitumor necrosis factor molecules, which were a breakthrough in IBD, improving mucosal healing and resection-free survival rate, other classes of therapeutic agents come to focus. Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent cellular immune response. In addition to anti-integrin antibodies, chemokine receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging results in clinical trials. Micro-RNAs have demonstrated their role as disease biomarkers but it could also become useful for the treatment of IBD. Moreover, cellular therapy is another therapeutic approach under development, aimed for severe refractory CD. Other experimental treatments include intravenous immunoglobulins, exclusive enteral nutrition, and granulocyte colony-stimulating factors.
慢性炎症性肠病（IBD）是胃肠病学中备受关注的课题，因为其病理机制难以解释，且尚未发现最佳治疗方法。克罗恩病（CD）是IBD的主要类型之一，其临床症状具有多态性，治疗反应差异很大。现代关于CD发病机制的理论已证明，肠道微生物群和环境因素会导致遗传易感性患者出现异常免疫反应。全球范围内对CD患者进行的全基因组关联研究发现了几种基因突变，这些突变会增加IBD的发病风险，并使疾病发展为更严重的病程。肠道微生物群被认为是CD发病机制中的一个必要且重要的部分。在所有IBD患者中都能发现肠道微生物失调，即存在过量的不同菌株。在CD患者切除组织中发现侵袭性大肠杆菌，这增加了抗菌或疫苗型治疗的可能性。最近针对肠道免疫学及其分子激活途径的研究为治疗提供了新的可能性。除了在IBD治疗中取得突破的抗肿瘤坏死因子分子（可改善黏膜愈合和无切除生存率）外，其他类别的治疗药物也受到关注。白细胞黏附抑制剂可阻断白细胞归巢机制，防止细胞免疫反应。除抗整合素抗体外，趋化因子受体拮抗剂和SMAD7反义寡核苷酸在临床试验中也显示出令人鼓舞的结果。微小RNA已证明其作为疾病生物标志物的作用，但它也可能对IBD的治疗有用。此外，细胞疗法是另一种正在开发的治疗方法，针对严重难治性CD。其他实验性治疗包括静脉注射免疫球蛋白、全肠内营养和粒细胞集落刺激因子。
