巴柳氮对葡聚糖硫酸钠结肠炎小鼠肠黏膜通透性的影响

目的探讨巴柳氮对结肠炎小鼠肠黏膜通透性的影响及其作用机制。方法将45只C57BL／6J小鼠分成正常对照组、葡聚糖硫酸钠（DSS）模型组、巴柳氮不同剂量组（42、141、423mg／kg），正常对照组自由饮水，其余各组自由饮用5％DSS溶液，巴柳氮灌胃给药。每日予以疾病活动指数（DAI）评分，实验结束后取结肠组织进行苏木精-伊红染色评分，匀浆检测髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、还原型谷胱甘肽活性（GSH-Px）、丙二醛（MDA）含量。小肠黏膜透射电镜检查。Evans蓝检测小肠黏膜通透性。结果与正常对照组小鼠相比，DSS组小鼠均出现明显的体质量减轻、便血和腹泻，DAI评分和病理（HI）评分增高（P〈0．01）。同时，结肠黏膜MPO活性和MDA含量明显增高（P〈0．05），SOD和GSH-Px活性明显降低。透射电镜检查小鼠回肠黏膜绒毛变短、萎缩、稀疏和排列极不规则，细胞间连接复合体缩短、变宽及细胞间隙扩大；小肠组织中Evans蓝含量增高。巴柳氮给药组小鼠一般情况明显改善，DAI评分与HI评分降低（P〈0．05），MPO活性减低，MDA含量降低，SOD和GSH-Px活性增高。随着巴柳氮剂量的增高，回肠黏膜微绒毛形态接近正常，小肠组织中Evans蓝含量明显减少。结论DSS模型小鼠肠黏膜通透陛增高，巴柳氮可改善结肠炎模型小鼠肠黏膜通透性。

Effect of balsalazide on intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

Objective To investigate the effect of balsalazide on intestinal mucosal permeability of experimental colitis induced by dextran sulfate sodium (DSS) in a mouse model and its possible mechanism. Methods Forty-five C57BL/6J mice were randomly divided into five groups. Normal group was only fed with distilled water, DSS group and Balsalazide groups at doses of 42,141,423 mg/kg were fed with 5% DSS. Balsalazide was given by intragastric administration. DAI was evaluated daily. At the end of the experiment, colon tissue was collected for assessment of histological changes, MDA content, MPO, SOD and GSH-PX activity. Small intestinal mucosa was collected for assessment of transmission electron microscope (TEM), and detection of permeability by Evans blue. Results Compared with normal group, DSS group mice all manifested severe weight loss associated with hematochezia and diarrhea with significant increase of DAI and HI score (P<0.01). MDA content and MPO activity was increased with the reverse result of SOD and GSH-PX (P<0.01) in DSS group. Intestinal mucosa showed a focal reduction in thinning of microvillons carpet and even a total disarrangement of epithelial surface, with decurtated and broaden junctional complex and enlarged intercellular space under TEM observations in DSS group. The amount of Evans blue permeated into intestinal wall was obvious in DSS group. Compared with DSS group, balsalazide improved gross findings, decreased MPO activity and MDA content, but increased the activity of SOD and GSH-PX (P<0.05). The amount of Evans blue permeated into intestinal wall was less (P<0.05). Ileal microvillous carpet was ameliorated in dose-dependent manner by balsalazide. Conclusions Intestinal mucosal permeability is increased in DSS group. Balsalazide can significantly ameliorate intestinal mucosal permeability in colitis model.