NF-κB抑制剂对烫伤脓毒症大鼠致炎/抗炎细胞因子表达的影响

Effects of NF-kappa B inhibition by pyrrolidine dithiocarbamate on tissue pro-and anti-inflammatory cytokine expression in rats with postburn Staphylococcus aureus sepsis

目的 观察NF κB抑制剂对动物主要器官致炎 /抗炎细胞因子基因及蛋白表达的调节效应 ,并对其作用机制进行初步探讨。方法 34只动物随机分为正常对照组 (n=6 )、烫伤 (2 0 %TBSAⅢ度 )对照组 (n=6 )、烫伤后金葡菌感染组 (n=12 )和NF κB抑制剂二硫氨基甲酸酞吡咯烷 (PDTC)拮抗组 (n =10 ) ,检测动物肝、肾、肺组织中TNF α、IL 10基因及蛋白表达的改变。结果 烫伤脓毒症组 0 5～2h肝、肺、肾组织中TNF αmRNA表达迅速增强 ,同时各组织TNF α蛋白水平亦显著升高。PDTC早期干预对肺脏TNF αmRNA及蛋白水平影响不明显 ,但肝、肾组织其表达量在 2h均被显著抑制 (P <0 0 5或 0 0 1)。烫伤合并金葡菌感染后 2h大鼠肝、肺、肾组织IL 10mRNA与蛋白水平均显著升高 (P <0 0 5或 0 0 1) ,早期给予PDTC对肺、肾组织各时间点IL 10mRNA与蛋白表达均无明显影响 ,肝组织仅 2h呈现一定程度地下降。结论 NF κB抑制剂在有效拮抗G+ 菌脓毒症TNF α等致炎介质的同时 ,对机体并存的抗炎细胞因子反应机制具有保护作用。

Objective To investigate the effects of inhibition of nuclear factor-kappa B (NF-κB) by pyrrolidine dithiocarbamate (PDTC) on tissue pro- and anti-inflammatory cytokine expression in rats with postburn Staphylococcus aureus sepsis and its potential regulating mechanism. Methods Thirty-four male Wistar rats were randomly divided into normal control group (n=6), scald control group (n=6), postburn sepsis group (n=12),and PDTC treatment group (n=10). Tissue samples from the liver, kidneys and lungs were collected to determine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) mRNA expression as well as their protein levels. Results Both TNF-α mRNA and protein expressions in the liver, kidneys and lungs of postburn septic animals were up-regulated rapidly at 0.5-2 hours (P<0.05 or 0.01). Treatment with PDTC could significantly inhibit TNF-α mRNA expression in the liver and kidneys, with an exception of the lungs, at 2 hours following septic challenge. Similarly, 2 hours after Staphylococcus aureus infection IL-10 mRNA and protein expressions in the liver, kidneys and lungs were elevated markedly (P<0.05 or 0.01). Early treatment with PDTC had no marked influence on IL-10 mRNA and protein expressions in various tissues, while hepatic IL-10 levels showed a tendency to decrease at 2 hours compared to those without PDTC treatment. Conclusion Treatment with NF-kB inhibitors can significantly down-regulate mRNA expression and protein levels of proinflammatory cytokines without marked influence on anti-inflammatory cytokines in vital organs after scald injury combined with Staphylococcus aureus challenge, and therefore it might attenuate the imbalance of cytokine response, thus it might be beneficial in prevention of development of postburn gram-positive bacterial sepsis.