高迁移率族蛋白B1抗体对结肠炎小鼠结肠黏膜的保护作用

Protective Role of Anti-high Mobility Group Box 1 Protein Antibody against Colonic Mucosa in Mice with Colitis

背景：我国溃疡性结肠炎（UC）发病率明显上升,但目前尚无满意的治疗方法,因此研究其发病机制并寻求新的治疗途径具有重要意义.目的：研究高迁移率族蛋白B1（HMGB1）抗体对结肠炎小鼠结肠黏膜的影响.方法：36只BALB/c小鼠随机分为正常对照组、结肠炎模型组和HMGB1抗体治疗组,后两组以3%葡聚糖硫酸钠（DSS）制备小鼠结肠炎模型,HMGB1抗体治疗组小鼠腹腔注射HMGB1抗体.实验第7 d,处死小鼠.行结肠组织学评分,测定结肠通透性,分别以RT-PCR和蛋白质印迹法检测结肠组织HMGB1 mRNA和蛋白表达.结果：与正常对照组相比,结肠炎模型组小鼠结肠组织学评分、结肠通透性以及HMGB1 mRNA和蛋白表达显著增高（P〈0.05）.与结肠炎模型组相比,HMGB1抗体治疗组小鼠结肠组织学评分、结肠通透性和HMCB1蛋白表达显著降低（P〈0.05）.结论：HMGB1参与了结肠炎小鼠的炎症反应过程,HMGB1抗体可有效抑制结肠炎小鼠结肠组织HMGB1表达,改善肠黏膜屏障功能,从而对UC结肠黏膜损伤起有明显保护作用.

Background： The incidence of ulcerative colitis （UC） is increasing in China, however, its therapy is not satisfactory, and therefore investigating its pathogenesis and looking for new medical treatment are crucial. Ahns： To investigate the effect of anti-high mobility group box 1 protein （HMGB1） antibody on colonic mucosa in mice with colitis. Methods： Thirty-six BALB/c mice were randomly divided into three groups： normal control group, colitis model group and anti-HMGB1 antibody treatment group. Colitis model was constructed by 3% dextran sulfate sodium （DSS） in the latter two groups. Mice in anti-HMGB1 antibody treatment group were given anti-HMGB1 antibody by intraperitoneal injection. On the 7~ day, the mice were sacrificed. Histological score of colon was evaluated, colonic permeability was determined. Expressions of HMGB1 mRNA and protein in colonic tissue were determined by RT-PCR and Western blotting, respectively. Results： Compared with normal control group, histological score of colon, colonic permeability and expressions of HMGB1 mRNA and protein were significantly increased in colitis model group （P〈0.05）. Compared with colitis model group, histological score of colon, colonic permeability and expression of HMGB1 protein were significantly decreased in anti-HMGB1 antibody treatment group （P〈0.05）. Conclusions： HMGB1 appears to be involved in the inflammatory process of colitis in mice. Treatment with anti-HMGB1 antibody can obviously inhibit colonic expression of HMGB1 and improve colonic mucosal barrier function, which show a protective role in colonic mucosal injury in UC.