TSP-2对小鼠溃疡性结肠炎NF-κB DNA结合活性和表达的影响  

TSP-2 suppresses the expression and DNA-binding activity of nuclear factor-κB p65 protein in mice with ulcerative colitis

作　　者：赖明广[1] 王立生[1] 姚君[1] 魏铖 

机构地区：[1]暨南大学第二临床医学院消化内科,广东深圳518020

出　　处：《南方医科大学学报》2013年第3期428-431,共4页Journal of Southern Medical University

基　　金：广东省自然科学基金(10151802001000002);深圳市重点科技计划项目(200901003)

摘　　要：目的研究抗小鼠Toll样受体2（Toll-like receptor 2）胞外段（mTLR2ECD）单表位抗体TSP-2对溃疡性结肠炎小鼠肠粘膜核因子NF-κB DNA结合活性和表达的影响。方法将实验小鼠随机分为4组：正常对照组、模型组、TSP-2治疗组和兔IgG组,其中模型组、TSP-2治疗组和兔IgG组均给予5%葡聚糖硫酸钠7 d以制备溃疡性结肠炎小鼠模型,停用造模药后TSP-2治疗组和兔IgG组给予后续干预治疗7 d。计算溃疡性结肠炎疾病活动指数（DAI）,14 d后处死小鼠,取结肠行HE染色;利用ELISA法测小鼠肠粘膜NF-κB P65 DNA结合活性;用Western blot法测定NF-κB p65蛋白水平,并进行统计学分析。结果模型组NF-κBp65 DNA结合活性明显高于对照组（P〈0.05）;模型组NF-κB P65蛋白表达明显高于NC组（P〈0.05）;TSP-2治疗组小鼠第10~14天DAI明显低于模型组（P〈0.05）;TSP-2治疗组NF-κB p65 DNA结合活性明显低于MD组（P〈0.05）;TSP-2治疗组NF-κBp65蛋白表达水平显著低于模型组（P〈0.05）;兔IgG组与模型组比较,实验结果无统计学意义（P〉0.05）。结论 TSP-2可以明显抑制NF-κB表达和活性,通过调节肠道过度的免疫反应和抗炎作用,在溃疡性结肠炎治疗中发挥作用。Objective To observe the effect of TSP-2, the antibody of Toll-like receptor 2 extracellular domain, on the expression and DNA-binding activity of nuclear factor-κB （NF-κB） p65 protein in mice with ulcerative colitis （UC）. Methods Sixty BALB/c mice were randomized equally into normal control group, UC model group, TSP-2 treatment group, and rabbit IgG treatment group. In the latter 3 groups, the mice were fed with 5% DSS （C6H7Na3O14S3） solution for 7 days to induced UC, followed then by treatment with daily injections of TSP-2 or rabbit IgG as appropriate for 7 days. The disease activity index was recorded during the treatment. The colitis tissues were collected after the treatments for HE staining and detecting the expression and DNA-binding activity of NF-κB p65 in the colon mucosa by Western blotting and ELISA. Results The DNA binding activity and expressions of NF-κB P65 protein increased significantly in UC model group （P〈0.05）. TSP-2 treatment group significantly decreased the disease activity index （P〈0.05） and lowered the DNA-binding activity and expression of NF-κB P65 protein （P〈 0.05） in the UC mouse models, while rabbit IgG produced no such effects （P〉0.05）. Conclusion TSP-2 can suppress the DNA-binding activity and protein expressions of NF-κB P65 and regulate excessive immune response in the intestines to ameliorate ulcerative colitis in mice.

关 键 词：溃疡性结肠炎 TSP-2 NF-ΚB 

分 类 号：R574.62[医药卫生—消化系统]