抗小鼠TLR2胞外段单表位抗体TSP-2对脓毒症小鼠肠粘膜核因子-κB和细胞因子表达的影响  

Effect of TSP-2 antibody against a single epitope of mouse Toll-like receptor 2 extracellular domain on nuclear factor-kappa B and cytokine expression in the intestine of septic mice

作　　者：黄恩平[1] 姚君[2] 杨翠兰[1] 罗深秋[1] 

机构地区：[1]南方医科大学基础医学院细胞生物学教研室,广东广州510515 [2]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》2011年第2期272-276,共5页Journal of Southern Medical University

基　　金：国家青年自然科学基金(30801032)~~

摘　　要：目的观察抗小鼠Toll样受体2胞外段(mTLR2ECD)单表位抗体TSP-2对脓毒症小鼠肠粘膜核因子-κB(NF-κB)和细胞因子表达的影响。方法将雄性BALB/c小鼠随机分成4组:假手术组、模型组、TSP-2治疗组和正常兔IgG治疗组。采用盲肠结扎穿孔术制作脓毒症小鼠模型,分别于术后6、12和24 h取回肠组织,HE染色,免疫组织化学方法检测小鼠肠粘膜组织NF-κB的表达,实时荧光定量RT-PCR法检测TNF-α和IL-6 mRNA的表达,ELISA法检测小鼠肠粘膜TNF-α和IL-6蛋白表达水平。结果模型组NF-κB表达水平较假手术组显著上升;TSP-2治疗组NF-κB表达水平较模型组显著下调;模型组各时间点TNF-α和IL-6水平均高于假手术组(P<0.05);TSP-2治疗组与模型组相比,TNF-α和IL-6水平明显降低(P<0.05),TNF-α和IL-6 mRNA水平也低于模型组(P<0.05)。正常兔IgG治疗组与模型组比较,结果无统计学意义(P>0.05)。结论抗体TSP-2能抑制脓毒症小鼠肠道NF-κB的活化,并下调致炎细胞因子TNF-α和IL-6水平,对脓毒血症引起的肠道炎症起到一定的控制作用,并延缓脓毒血症的病情发展。Objective To observe the effect of the antibody TSP-2 against a single epitope of mouse Toll-like receptor 2 extracellular domain（mTLR2ECD） on the expression of nuclear factor-kappa B（NF-κB） and cytokines in the intestinal tissue of septic mice.Method Male BALB/c mice were randomly divided into 4 groups,namely the sham-operated group,model group,TSP-2 treatment group and rabbit IgG treatment group.Sepsis was induced by cecal ligation and puncture（CLP）,and at 6,12 or 24 h after the operation,the ileal tissues were harvested from the mice for HE staining.NF-κB expression was detected with immunohistochemistry.Tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） mRNA expressions were detected with qRT-PCR and their protein expressions by ELISA.Results The NF-κB expression in the intestinal tissue significantly increased in the model group as compared with that in the sham-operated group,and decreased after TSP-2 treatment.The model group also showed significantly increased expression levels of TNF-α and IL-6 mRNA and protein in the intestinal tissue（P0.05）,which were lowered by TSP-2（P0.05） but not by rabbit IgG treatment（P0.05）.Conclusion The TSP-2 antibody can protect the intestine and delay the development of sepsis by inhibiting NF-κB activation and down-regulating TNF-α and IL-6 expressions in mice.

关 键 词：脓毒症 TOLL样受体2 TSP-2 核因子-ΚB 细胞因子 肿瘤坏死因子-α 白细胞介素-6 

分 类 号：R459.7[医药卫生—急诊医学]