英夫利西单克隆抗体对克罗恩病患者肠黏膜屏障功能修复的研究  

Study on the repairation of intestinal mucosal barrier by infliximab in patients with Crohn′s disease

作　　者：赵玉洁 王奕文[2] 王东 孙晓敏 刘占举[3] Zhao Yujie;Wang Yiwen;Wang Dong;Sun Xiaomin;Liu Zhanju(Department of Gastroenterology,Chongming Branch of Shanghai Tenth People′s Hospital,Shanghai 202157,China;Electron Microscope Center of East China Normal University,Shanghai 200062,China;Department of Gastroenterology,Shanghai Tenth People′s Hospital,Shanghai 200072,China)

机构地区：[1]上海市第十人民医院崇明分院消化内科,202157 [2]华东师范大学电镜中心,上海200062 [3]上海市第十人民医院消化内科,200072

出　　处：《中华消化杂志》2020年第8期524-531,共8页Chinese Journal of Digestion

基　　金：上海市崇明区"可持续发展科技创新行动计划"(CKW2018-26)。

摘　　要：目的探讨英夫利西单克隆抗体(IFX)对CD患者肠黏膜屏障的修复作用。方法选择2018年1月至2019年10月于上海市第十人民医院就诊的CD患者382例,均行IFX治疗,另选择103名行结肠镜检查者作为健康对照组。收集CD患者和健康对照者的一般临床资料、空腹血和肠黏膜组织样本,计算BMI,检测血红蛋白、白蛋白、ESR、CRP,以及相关炎症因子TNF-α、γ干扰素、IL-1、IL-2、IL-6、IL-8、IL-10、IL-17A表达水平及其mRNA水平。采用克罗恩病疾病活动指数(CDAI)和克罗恩病简化内镜评分(SES-CD)评价CD患者的疾病活动度。采用蛋白质印迹法分析闭锁蛋白、紧密连接蛋白-1、闭锁小带蛋白-1(ZO-1)和连接黏附分子-A(JAM-A)表达水平。通过透射电子显微镜观察肠黏膜上皮细胞。统计学分析采用t检验。结果CD患者治疗前BMI、血红蛋白、白蛋白水平均低于健康对照组[(18.3±1.8)kg/m^2比(20.2±1.2)kg/m^2、(95.3±8.4)g/L比(129.2±5.7)g/L、(33.2±5.4)g/L比(50.3±3.2)g/L],差异均有统计学意义(t=3.457、5.342、2.674,P均<0.05)。CD患者治疗后BMI和血红蛋白水平均高于治疗前[(19.5±2.1)kg/m^2比(18.3±1.8)kg/m^2、(117.2±10.3)g/L比(95.3±8.4)g/L],CRP水平、CDAI评分、SES-CD评分均低于治疗前[(16.3±2.3)mg/L比(47.2±9.3)mg/L、(113.2±12.5)分比(245.2±23.5)分、(5.0±2.1)分比(10.0±4.3)分],差异均有统计学意义(t=2.090、2.339、2.432、6.345、5.234,P均<0.05)。健康对照组促炎因子TNF-α、γ干扰素、IL-2、IL-6、IL-8、IL-17A表达水平及其mRNA水平均低于CD患者治疗前[分别为(1.1±0.4)ng/L比(158.2±38.3)ng/L、(3.2±0.8)ng/L比(28.3±13.4)ng/L、(2.7±1.3)ng/L比(3.3±2.4)ng/L、(5.2±0.3)ng/L比(16.3±7.4)ng/L、(16.3±6.3)ng/L比(18.9±10.2)ng/L、(10.5±2.3)ng/L比(38.5±11.2)ng/L;1.00±0.00比4.68±0.34、7.83±0.32、1.25±0.46、8.36±0.44、2.01±0.89、6.83±0.53],差异均有统计学意义(t=2.345、6.456、3.008、4.009、7.045、10.223,8.345、11.235、1.114、12Objective To explore the role of infliximab(IFX)in the repairation of intestinal mucosal barrier in Crohn′s disease(CD).Methods From January 2018 to October 2019,in Shanghai Tenth People′s Hospital,382 CD patients were selected.All the patients were treated with IFX.And 103 individuals who underwent colonoscopy were selected as healthy control group.The general clinical data,fasting blood samples and intestinal mucosa tissue samples of CD patients and healthy controls were collected.The body mass index(BMI),hemoglobin,albumin,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)and relative inflammation factors,including tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-1,IL-2,IL-6,IL-8,IL-10 and IL-17A,and their mRNA expression levels were detected.Crohn′s disease activity index(CDAI)and simplified endoscopic score for Crohn′s disease(SES-CD)were used to evaluate the disease activity of CD patients.The expression levels of occudin,claudin-1,zonula occluden-1(ZO-1)and junctional adhesion molecule-A(JAM-A)were measured by Western blotting.The intestinal mucosal epithelial cells were observed by transmission electron microscope.T test was used for statistical analysis.Results Before treatment,BMI,and hemoglobin and albumin levels of CD patients were all lower than those of healthy control group((18.3±1.8)kg/m^2 vs.(20.2±1.2)kg/m^2,(95.3±8.4)g/L vs.(129.2±5.7)g/L,(33.2±5.4)g/L vs.(50.3±3.2)g/L),and the differences were statistically significant(t=3.457,5.342 and 2.674,all P<0.05).After treatment the BMI and hemoglobin levels of CD patients were higher than those before treatment((19.5±2.1)kg/m^2 vs.(18.3±1.8)kg/m^2,(117.2±10.3)g/L vs.(95.3±8.4)g/L),and the CRP level,CDAI score and SES-CD score were lower than those before treatment((16.3±2.3)mg/L vs.(47.2±9.3)mg/L,113.2±12.5 vs.245.2±23.5,5.0±2.1 vs.10.0±4.3),and the differences were statistically significant(t=2.090,2.339,2.432,6.345 and 5.234,all P<0.05).The expression levels of TNF-α,IFN-γ,IL-2,IL-6,IL-8,IL-17A and t

关 键 词：CROHN病 英夫利西单抗 肠黏膜屏障 肠上皮紧密连接 

分 类 号：R574.62[医药卫生—消化系统]