JAK/STAT通路对烫伤脓毒症大鼠Toll样受体基因表达的调节作用

Potential role of JAK/STAT in regulating Tolllike receptor 2 gene expression in rats with postburn Staphylococcus aureus sepsis

目的 :探讨 Janus激酶 /信号转导和转录激活子 ( JAK/ STAT)通路在烫伤脓毒症大鼠 Toll样受体 2( TL R2 )基因表达调控中的意义。方法 :Wistar大鼠 38只随机分为正常对照组 ( n=6 )、烫伤后金黄色葡萄球菌(金葡菌 )感染组 ( n=12 )、AG490拮抗组 ( n=10 )和雷帕霉素 ( Rapam ycin,RPM)拮抗组 ( n=10 ) ,检测动物肝、肾、肺组织中 TL R2和肿瘤坏死因子 α( TNFα)基因表达的改变。结果 :烫伤合并金葡菌攻击后 0 .5 h和 2 h,动物肝、肾、肺组织中 TL R2 m RNA表达显著增高 ( P<0 .0 5或 P<0 .0 1)。RPM干预可有效抑制动物肝、肾组织 TL R2 m RNA表达 ,但对肺脏 TL R2 m RNA表达无明显影响 ;而 AG490拮抗组动物各组织中 TL R2 m RNA表达与未干预组相比均无明显差异。烫伤合并金葡菌感染后 2 h大鼠肝、肺、肾组织 TNFα基因表达均显著升高 ( P均 <0 .0 1)。给予 RPM可明显抑制各组织中 TNFα m RNA表达 ( P<0 .0 5或 P<0 .0 1) ,AG490拮抗组大鼠肝、肾组织中 TNFα表达亦均显著低于未拮抗组 ( P均 <0 .0 1)。结论 :烫伤后金葡菌感染可促进体内TL R2基因表达 ,STAT可能直接或通过其诱生的炎症介质参与了对 TL R2 m RNA表达的调控。

Objective:To investigate the potential role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway in regulating Tolllike receptor 2 (TLR2) gene expression in postburn Staphylococcus aureus infection.Methods:Thirtyeight male Wistar rats were randomly divided into four groups as follows:normal control group (n=6),postburn sepsis group (n=12),AG490 treatment group (n=10) and Rapamycin (RPM) treatment group (n=10).Tissue samples from the liver, kidneys and lungs were collected to determine TLR2 and TNFα mRNA expressions.Results:It was found that,0 5 and 2 hours after Staphylococcus aureus challenge,TLR2 mRNA expressions in the liver, kidneys and lungs from postburn septic animals were upregulated rapidly (P<0 05 or P<0 01).Treatment with RPM could effectively inhibit TLR2 mRNA expressions in the liver and kidneys.However,TLR2 mRNA expressions in the above tissues from AG490 treated animals had no significant differences with those from normal controls. Two hours after Staphylococcus aureus challenge,TNFα mRNA expressions in the liver, kidneys and lungs were also increased markedly (all P<0 01).Both treatment with RPM and AG490 could significantly inhibit the upregulation of all tissue TNFα mRNA expressions (P<0 05 or P<0 01),and AG490 were more significant in liver and kidneys(both P<0 01).Conclusion:It is suggested that scald injury combined with Staphylococcus aureus infection can upregulate TLR2 expression,which appears to be associated with the signal transduction of STAT.