烫伤后金葡菌脓毒症大鼠Toll样受体2基因表达及其信号机制的研究

SIGNIFICANCE OF CHANGES IN Toll-LIKE RECEPTOR 2 IN RATS WITH POSTBURN STAPHYLOCOCCUS AUREUS SEPSIS AND ITS POTENTIAL SIGNAL TRANSDUCTION

采用大鼠 2 0 %Ⅲ度烫伤合并金葡菌攻击所致脓毒症模型 ,观察Toll样受体 2 (TLR2 )在主要器官中的变化特点及意义 ,初步探讨了信号通路抑制剂对TLR2及炎症介质表达的影响。68只大鼠随机分为正常对照组 (n =6)、烫伤对照组 (n =6)、烫伤后金葡菌感染组 (n =3 6)、AG12 6拮抗组 (n =10 )和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TLR2和TNF α基因表达的变化。结果显示 ,烫伤合并金葡菌攻击后 ,动物肝、肾、肺组织中TLR2mRNA表达均迅速增高 ,分别于 0 5～ 2h达峰值 (P <0 0 5～0 0 1) ,此后有所降低 ;PDTC干预可在一定程度上下调肾脏TLR2mRNA表达 (P <0 0 5 )。伤后 0 5h和 2h ,AG12 6拮抗组动物肾脏和肝脏TLR2mRNA表达也明显受抑 (P <0 0 5 )。烫伤合并金葡菌感染后 2h大鼠肝、肺、肾组织TNF α基因表达显著升高 (P <0 0 5 ) ,PDTC和AG12 6则对此有抑制作用 (P<0 0 5 )。提示烫伤后金葡菌感染可促进体内TLR2基因表达 ,后者作为细菌致病因子跨膜信号转导的重要受体在烫伤脓毒症的发生。

To investigate changes in Toll-like receptor 2 (TLR2) gene expression in postburn Staphylococcus aureus infection, and its potential signaling mechanism, 68 male Wistar rats were randomly divided into four groups as follows: normal control group (n=6), scald control group (n=6), postburn sepsis group (n=36),AG126 treatment group (n=10) and pyrrolidine dithiocarbamate (PDTC) treatment group (n=10). Tissue samples from the liver, kidney and lung were collected from every group to determine TLR2 and tumor necrosis factor-α (TNF-α) mRNA expression. The results showed that TLR2 mRNA expressions in the liver, kidney and lung from postburn septic animals were up-regulated rapidly, peaking at 0.5-2 hours (P<0.01), then decreased. Twenty-four hours after Staphylococcus aureus challenge, TLR2 mRNA expressions in the liver and kidney returned to the baseline, while those in the lung remained at a high level. Treatment with PDTC could effectively inhibit TLR2 mRNA expression in kidneys. Renal and hepatic TLR2 mRNA expressions in AG126-treated animals were also inhibited to a certain extent at 0.5 and 2h after sepsis (P<0.05, compared with postburn sepsis group). Similarly, 2h after Staphylococcus aureus infection TNF-α mRNA expressions in the liver, kidney and lung were up-regulated markedly (P<0.05). Both PDTC and AG126 treatment effectively inhibited the elevation of TNF-α mRNA expression in various tissues. These results suggested that scald injury combined with Staphylococcus aureus challenge could up-regulate TLR2 expression in vital organs, which, acts as a trans-membrane signal transduction receptor of bacterial component, might be involved in the pathogenesis of postburn sepsis.