髓系触发受体-1在脆弱类杆菌诱导小鼠脓毒血症中的作用
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黄晓元

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Effect of TREM-1 in sepsis caused by bacteroides fragilis in mice
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    摘要:

    目的:探讨小鼠TREM-1基因重组慢病毒干扰载体(Lentivector,LV)TREM-1vshRNA对脆弱杆菌脓毒血症小鼠脾脏中促炎症因子TNF-α,IL-1β,IL-6表达及NF-κB通路的影响。
    方法:将清洁级BALB/c雄性小鼠分成4组,即正常对照组(C组),脆弱类杆菌脓毒症模型生理盐水组(S组),TREM-1vshRNA干扰实验组(T组)和 GFPvshRNA干扰实验组(G组)。观察各组中小鼠脾内TREM-1,TNF-α, IL-1β, lL-6的蛋白表达以及IkBa, pDAP12,NF-κB p65的表达情况的变化。
    结果:与C组比,T组TREM-1mRNA及蛋白表达均有显著增加(P<0.01); T,G,S组脾细胞中TNF-α,IL-1β,IL-6的含量均较C组显著增加(P<0.01); T组脾细胞中TNF-α,IL-1β,IL-6的含量均较S,G组明显降低(P<0.01)。S组脾细胞中的pDAP12和核内NF-κB p65蛋白表达水平明显增强,IκBa蛋白表达水平降低; 而T组与S组比较,pDAP12和NF-κB p65蛋白的表达水平显著下调。
    结论:小鼠TREM-1基因重组慢病毒干扰载体可选择性抑制TREM-1表达,下调脆弱类杆菌诱导的促炎症因子的分泌,而转染可能是通过下调DAP12的表达,稳定IkBa/NF-κB复合物,抑制TNF-α,IL-1β,IL-6,IL-8基因的转录,而对脆弱类杆菌脂多糖炎症反应产生抑制作用。

    Abstract:

    Objective:To explore the effect and the mechanism of TREM-1vshRNA in the form of sepsis in mice caused by live bacteroides fragilis and the expression of TNF-α, IL-1β, IL-6 and IL-8.
    Methods :Male mice(BALB/c) were randomly divided into 4 groups: positive control (group C), saline(group S),TREM-1vshRNA(group T) and GFPvshRNA control vshRNA (group G) groups. Bacteroides fragilis (25mg/ kg) was injected via caudal veins in each group to establish the murine septic model. The expression of TREM-1, tumor necrosis factor alpha (TNF-α), IL-1β,lL-6, IkBa, pDAP12 and NF-κBp65 in spleen was observed in each group.
    Results:In comparison with group C there was marked elevation of expession of TREM-1mRNA and protein in group T (P<0.01).Compared to group C there was marked elevation of TNF-α, IL-1β and IL-6 content in splenic cells of groups T,G and S (P<0.01).The level of TNF-α, IL-1β and IL-6 in splenic cells of group T was markedly lower than that of groups S and G (P<0.01).In splenic cells of group S,pDAP12 and NF-κBP 65 protein expression was markedly increased compared to group T; the expression of 1κBa protein in splenic cells of groups was decreased.
    Conclusions:The interference of TREM-1 signal pathway by TREM-1vshRNA may inhibit the genetic transcriptions of inflammatory factors, such as TNF-α,IL-1β ,IL-6 by downregulating the expression of DAP12, so to stablize the compound of IkBa/NF-κB, can inhibit the inflammatory reaction induced by Bacteroides fragilis.

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宋达疆, 黄晓元, 杨兴华, 肖目张, 王双.髓系触发受体-1在脆弱类杆菌诱导小鼠脓毒血症中的作用[J].中国普通外科杂志,2009,18(2):13-.
DOI:10.7659/j. issn.1005-6947.2009.02.013

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  • 在线发布日期: 2009-02-25