摘要
目的探讨Toll样受体(TLRs)信号途径负性调节因子在小儿脓毒症异常炎症反应发病机制中的可能作用。方法以脓毒症患儿10例、严重全身性感染患儿13例为研究对象,采用实时荧光定量PCR检测TLRs途径传导分子、负性调节因子及前炎症细胞因子mRNA表达;ELISA法检测前炎症细胞因子水平。结果(1)脓毒症患儿前炎症因子IL-1β、IL-6、TNF-αmRNA表达及蛋白水平明显高于对照组(P〈0.01);(2)脓毒症患儿TLRs信号传导途径分子TLR2、TLR4、MyD88、TRAF6、IRAK4、TAB2及TAK1mRNA表达明显增高(P〈0.01);(3)脓毒症患儿TLRs负性调节因子SIGIRR、DAP12和FLN29mRNA表达增高,严重脓毒症组表达低于脓毒症组(P〈0.01)。结论TLRs信号传导途径传导分子及负性调节因子异常表达可能是脓毒症全身性炎症反应综合征的原因之一。
Objective To investigate role of negative regulatory factors of signal pathways of Toll-like receptors (TLRs) in aberrant inflammatory response of septic children. Methods Peripheral blood mononuclear cell (PBMC) and serum were obtained from 10 children with sepsis, 13 children with severe sepsis and 17 age-matched healthy controls. Real time-PCR were used to evaluated the mRNA levels of TLR2, TLR4, MyD88, IRAK-4, TRAF6, TAB2 TAK1, SIGIRR, DAP12, FLN29, IL-1, IL-6 and TNF-α. Pro-inflammatory cytokines( IL-1, IL-6 and TNF-α) were measured by enzyme-linked immunosorbnent assay(ELISA). Results (1) Compared with the healthy control groups, gene expression and protein levels of pro-inflammatory cytokine(IL-1, IL-6 and TNF-α) were significantly increased in sepsis groups and severe sepsis groups(P 〈 0.01 ). (2) Compared with the healthy control group, the levels of mRNA expression of TLRs signal pathway molecules (TLR2, TLR4, MyD88, TRAF6, IRAK4, TAB2 and TAK1 ) were significantly increased in sepsis groups and severe sepsis groups(P 〈 0.01). (3) Compared with the healthy control groups, the mRNA expression levels of negative regulators of TLRs pathways( ISIGIRR, DAP12 and FLN29) were significantly increased in sepsis groups, but the expression levels of these negative regulator in severe sepsis groups were significantly decreased than those in sepsis groups(P 〈 0.01 ). Conclusion Aberrant activation of TLRs pathways and aberrant expression of the negative regulators in TLR-like receptor signaling might play an important role in the development of abnormal inflammatory response in septic children.
出处
《中国小儿急救医学》
CAS
2008年第5期423-426,共4页
Chinese Pediatric Emergency Medicine
关键词
脓毒症
TOLL样受体
调节因子
全身炎症反应综合征
儿童
Sepsis
Toll-like receptor
Regulatory factor
Systemic inflamatory response syndrome
Children