Gong Yi, Li Hui, Li Yan
Department of Gastroenterology, Shengjing Hospital, China Medical University , Shenyang, China .
J Interferon Cytokine Res. 2016 Feb;36(2):75-85. doi: 10.1089/jir.2015.0030. Epub 2015 Dec 31.
Intestinal mucosal barrier dysfunction associated with inflammatory bowel disease (IBD). Effects of Bacillus subtilis on epithelial tight junctions (TJs) and intrinsic regulatory mechanisms of the intestine were studied in pursuit of better treatments for IBD. Fifty Balb/c mice given 5% dextran sulfate sodium (DSS) in tap water ad libitum over a 7-day period (to induce colitis) were randomly assigned to 4 test groups [DSS, DSS+B. subtilis, DSS+5 amino salicylic acid (5ASA), and DSS+B. subtilis+5ASA] to compare with normal controls. In the test groups DSS was administered daily by oral gavage in normal saline (0.2 mL), adding B. subtilis (1 × 10(8) CFU), 5ASA (6 mg), or both for respective test groups. Defecation, body weight, colitis score, pathological features, epithelial TJs proteins [claudin-1, occludin, junctional adhesion molecule (JAM)-A, and zona occludens (ZO)-1], and various cytokines [interleukin (IL)-6, IL-17, IL-23, and tissue necrosis factor (TNF)-α] were evaluated. Relative to the DSS group, disease activity index scores, and graded histologic damage were all significantly reduced by B. subtilis intake. All parameters declined even further when B. subtilis and 5ASA were combined. Analytic testing (immunohistochemical, western blot, and PCR) revealed progressive increase in TJ protein (claudin-1, occludin, JAM-A, and ZO-1) expression in DSS, DSS+B. subtilis, DSS+5ASA, DSS+B. subtilis+5ASA, and normal control groups (P < 0.05), whereas cytokine (IL-6, IL-17, IL-23, and TNF-α) expression similarly declined (P < 0.05). B. subtilis intake upregulated expression of TJ proteins (claudin-1, occludin, JAM-A, and ZO-1), for improved barrier function, and downregulated cytokine expression (IL-6, IL-17, IL-23, and TNF-α) to reduce intestinal epithelial damage.
肠道黏膜屏障功能障碍与炎症性肠病（IBD）相关。为寻求更好的IBD治疗方法，研究了枯草芽孢杆菌对上皮紧密连接（TJ）和肠道内在调节机制的影响。50只Balb/c小鼠在7天内随意饮用含5%葡聚糖硫酸钠（DSS）的自来水（以诱导结肠炎），然后随机分为4个试验组[DSS组、DSS+枯草芽孢杆菌组、DSS+5-氨基水杨酸（5ASA）组和DSS+枯草芽孢杆菌+5ASA组]，与正常对照组进行比较。在试验组中，每天通过口服灌胃给予DSS（溶于0.2 mL生理盐水中），并分别为相应试验组添加枯草芽孢杆菌（1×10⁸CFU）、5ASA（6 mg）或两者。评估了排便情况、体重、结肠炎评分、病理特征、上皮TJ蛋白[闭合蛋白-1、闭锁蛋白、连接黏附分子（JAM）-A和闭合小带（ZO）-1]以及各种细胞因子[白细胞介素（IL）-6、IL-17、IL-23和组织坏死因子（TNF）-α]。与DSS组相比，摄入枯草芽孢杆菌可显著降低疾病活动指数评分和组织学损伤分级。当枯草芽孢杆菌和5ASA联合使用时，所有参数进一步下降。分析检测（免疫组织化学、蛋白质印迹和PCR）显示，DSS组、DSS+枯草芽孢杆菌组、DSS+5ASA组、DSS+枯草芽孢杆菌+5ASA组和正常对照组中TJ蛋白（闭合蛋白-1、闭锁蛋白、JAM-A和ZO-1）表达逐渐增加（P<0.05），而细胞因子（IL-6、IL-17、IL-23和TNF-α）表达同样下降（P<0.05）。摄入枯草芽孢杆菌上调了TJ蛋白（闭合蛋白-1、闭锁蛋白、JAM-A和ZO-1）的表达，以改善屏障功能，并下调细胞因子表达（IL-6、IL-17、IL-23和TNF-α），以减少肠道上皮损伤。
