核苷酸寡聚化结构域2相关肠屏障损伤在回肠贮袋炎中的作用

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目的:观察并分析贮袋炎患者的肠屏障功能,探索核苷酸寡聚化结构域2(NOD2)蛋白在回肠贮袋炎中的作用,为研究UC并发贮袋炎的发病机制提供新的思路。方法:回顾性分析2011年1月至2016年12月在天津医科大学总医院内镜中心行贮袋黏膜活组织检查的回肠贮袋肛管吻合术后患者的临床病理资料,根据贮袋炎疾病活动度指数将患者分为贮袋炎组(20例)和非贮袋炎组(30例)。另选择未行手术治疗的UC患者为对照组(10例)。使用透射电子显微镜观察贮袋炎组和非贮袋炎组患者的肠腔结构,采用免疫组织化学技术检测并计算对照组、非贮袋炎组和贮袋炎组患者的闭合蛋白、α人防御素和NOD2的阳性表达率。统计学方法采用Levene检验、独立样本n t检验和Spearman相关分析。n 结果:透射电子显微镜下见贮袋炎组患者的肠黏膜上皮紧密连接结构和腔面微线毛损伤严重。免疫组织化学结果显示,贮袋炎组患者肠黏膜中闭合蛋白、α人防御素和NOD2的阳性表达率均低于对照组和非贮袋炎组[分别为(19.3±0.4)%比(84.0±0.3)%和(77.9±0.5)%,(60.0±1.3)%比(85.0±0.1)%和(77.3±0.4)%,(46.1±1.6)%比(72.0±0.7)%和(60.7±0.5)%],差异均有统计学意义(n t=-8.451、-7.514,-3.943、-2.970,-5.115、-2.982;n P均<0.05)。相关性分析显示,NOD2的表达水平与闭合蛋白、α人防御素呈正相关(n r=0.671、0.628,n P均<0.01)。n 结论:回肠贮袋炎患者肠屏障功能受损,NOD2相关的肠屏障损伤可能在回肠贮袋炎发病机制中处于重要地位。“,”Objective:To observe and analyze the function of intestinal barrier in patients with pouchitis, and to explore the role of nucleotide oligomerization domain 2 (NOD2) in ileal pouchitis, so as to provide new ideas for the pathogenesis of pouchitis.Methods:From January 2011 to December 2016, the clinical pathological data of patients with ileal pouch-anal anastomosis who underwent pouch mucosa biopsy at the Endoscopy Center of General Hospital of Tianjin Medical University were retrospectively analyzed. According to the disease activity index of pouchitis, patients were divided into pouchitis group (20 cases) and non-pouchitis group (30 cases). In addition, UC patients who did not undergo surgery were selected as the control group (10 cases). The intestinal structure of patients of the pouchitis group and non-pouchitis group was observed under transmission electron microscope. The positive expression rates of occludin, alpha human defensin and NOD2 in the control group, non-pouchitis group and pouchitis group were detected and calculated by immunohistochemistry. Levene test, independent sample n t test and Spearman correlation analysis were used for statistical analysis.n Results:Under the transmission electron microscope, the tight junction epithelial structure and microvilli of intestinal mucosal of patients in the pouchitis group were severely injured. The results of immunohistochemistry showed that the positive expression rates of occludin, alpha human defensin and NOD2 in the intestinal mucosa of patients in the pouchitis group were all lower than those of the control group and non-pouchitis groups ((19.3±0.4)% vs. (84.0±0.3)% and (77.9±0.5)%; (60.0±1.3)% vs. (85.0±0.1)% and (77.3±0.4)%; (46.1±1.6)% vs. (72.0±0.7)% and (60.7±0.5)%), and the differences were statistically significant (n t=-8.451, -7.514, -3.943, -2.970, -5.115 and -2.982, all n P<0.05). The correlation analysis showed that the expression level of NOD2 was positively correlated with occludin and alpha human defensin (n r=0.671 and 0.628, both n P<0.01).n Conclusions:Intestinal barrier function is impaired in patients with ileal pouchitis, and NOD2-related intestinal barrier injury may play an important role in the pathogenesis of ileal pouchitis.
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