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《Journal of Applied Clinical Pediatrics》 2012-24
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Effect of Extracellular Signal Regulated Kinase Inhibitor PD98059 on Expression of Tumor Necrosis Factor-α in Brain Tissue in Neonatal Rats with Sepsis

WANG Jing,LI Xi-hong,QU Yi,LIU Zhong-qiang,PAN Ling-li,WANG Yan,WANG Hui-qing,MU De-zhi(Department of Emergency Medicine,West China Second University Hospital of Sichuan University,Chengdu 610041,Sichuan Province,China)  
Objective To investigate the expression of inflammatory cytokines TNF-α in brain tissue of rats with sepsis and the effect of extracellular signal regulated kinase(ERK) inhibitor PD98059 on its expression.Methods Models of neonatal rats with sepsis were established by the cecal ligation and puncture(CLP).Totally 74 cases of 10-day-old neonatal rats were randomly divided into 3 groups:control group(n=6),CLP group(n=34) and PD98059 group(n=34).In CLP group,only CLP was performed in the rats.In PD98059 group,PD98059(0.3 mg·kg-1 body weight) was injected into the rats peritoneal cavity 0.5 hour before CLP.Six rats in CLP group and PD98059 group were killed and their brains were removed at 2 h,4 h,6 h and 8 h after CLP,respectively.Then,reverse transcriptase polymerase chain reaction was used to detect the TNF-α mRNA expression in rats′ brain tissue.Expression of protein was detected by the enzyme linked immunosorbent assay.Results In control group,there were very low expressions of TNF-α mRNA and protein in rats′ brain tissue.In CLP group,the expressions of TNF-α mRNA and protein started to increase at 2 hours,reached the peak at 6 hours and decreased at 8 hours after CLP,and were up-regulated significantly compared with control group(P0.001,0.05).Expressions of TNF-α mRNA and protein were significantly lower in various time points after CLP in PD98059 group than those in CLP group(Pa0.001,0.05).Additionally,10 cases in the other 20 rats with sepsis died in 10 days,including 8 cases in CLP group(mortality rate,80%) and 2 cases in PD98059 group(mortality rate,20%)(P=0.023).Conclusions In the early stage,sepsis can induce the prominent increased expression of TNF-α in brain tissue of neonatal rats.But ERK inhibitor PD98059 can down-regulate its expression,and alleviate the brain injury as well as reduce septic mortality.
【Fund】: 教育部长江学者和创新团队发展计划(IRT0935);; 国家自然科学基金(30500544);; 四川省科技厅支撑项目(2012SZ0012)
【CateGory Index】: R722.1
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