Departamento de Cirurgia, Faculdade de Ciências Médicas, Unicamp, Campinas - São Paulo - Brasil.
Departamento de Cirurgia, Universidade São Francisco, Bragança Paulista - São Paulo - Brasil.
Arq Bras Cir Dig. 2022 Jan 31;34(4):e1639. doi: 10.1590/0102-672020210002e1639. eCollection 2022.
The etiopathogenesis of disuse colitis (DC) has not yet been fully elucidated. The main theories consider that the disease may be related to an increase in anaerobic bacteria, the lack of short-chain fatty acid (SCFA) supply, and immunological disorders that develop in the colorectal segments devoid of fecal transit. The aim of this study was to verify whether the application of infliximab modifies the tissue content of E-cadherin and claudin-3 proteins in colonic epithelium of rats devoid of intestinal transit.
A total of 22 rats underwent intestinal transit bypass using Hartmann's procedure. They remained with the shunt for 12 weeks to allow the development of DC. Later, they were divided into three experimental groups: six animals received 2.0 mL saline solution/week, eight received infliximab at a dose of 5 mg/kg/week, and eight received infliximab at a dose of 10 mg/kg/week for 5 consecutive weeks. At the end of this period, the animals were euthanized, and the colonic segments with and without intestinal transit were removed. DC was diagnosed based on the histological changes defined by a previously validated scale. The tissue expression of E-cadherin and claudin-3 was assessed by immunohistochemistry, and the tissue content of both proteins was quantified by computer-aided image analysis.
The colonic segments excluded from fecal transit showed a higher degree of inflammation than those exposed to fecal transit. The degree of inflammation was lower in animals treated with infliximab, regardless of the dose used. The levels of E-cadherin and claudin-3 were reduced in the excluded colon. Treating animals with infliximab increased the levels of both proteins in the colonic segments without intestinal transit, especially in animals receiving a dose of 10 mg/kg/week.
Infliximab therapy reduces inflammation in the colonic segments excluded from intestinal transit and increases the tissue content of E-cadherin and claudin-3 proteins, especially when used at a concentration of 10 mg/kg/week.
失用性结肠炎（DC）的发病机制尚未完全阐明。主要理论认为，疾病可能与厌氧菌增加、短链脂肪酸（SCFA）供应不足以及缺乏粪便转运的结直肠段发生的免疫紊乱有关。本研究旨在验证英夫利昔单抗的应用是否会改变无肠道转运大鼠结肠上皮组织中 E-钙黏蛋白和紧密连接蛋白 3 蛋白的含量。
共 22 只大鼠采用哈特曼术进行肠道转运旁路。他们带着分流器 12 周，以允许 DC 发展。之后，他们被分为三个实验组：六只动物每周接受 2.0 mL 生理盐水/周，八只动物每周接受英夫利昔单抗 5mg/kg/周，八只动物每周接受英夫利昔单抗 10mg/kg/周，连续 5 周。在此期间结束时，处死动物，取出有和无肠道转运的结肠段。根据之前验证的评分标准，通过组织学变化诊断 DC。通过免疫组织化学评估 E-钙黏蛋白和紧密连接蛋白 3 的组织表达，并通过计算机辅助图像分析定量两种蛋白的组织含量。
与暴露于粪便转运的结肠段相比，排除粪便转运的结肠段表现出更高程度的炎症。无论使用何种剂量，用英夫利昔单抗治疗的动物炎症程度均较低。在排除的结肠中，E-钙黏蛋白和紧密连接蛋白 3 的水平降低。用英夫利昔单抗治疗动物增加了无肠道转运的结肠段中这两种蛋白的水平，尤其是在接受 10mg/kg/周剂量的动物中。
英夫利昔单抗治疗可减轻排除肠道转运的结肠段的炎症，并增加 E-钙黏蛋白和紧密连接蛋白 3 蛋白的组织含量，尤其是在使用 10mg/kg/周的浓度时。
