阻滞ERK1/2通路对大鼠弥漫性脑损伤组织c-fos基因表达的影响

目的 研究大鼠弥漫性脑损伤（DBI）后细胞外信号调节激酶1／2（ERK1／2）通路特异性阻断剂U0126对c-fos基因表达的影响。方法 按Marmarou方法制作大鼠DBI模型，尾静脉注射U0126。Western blot法检测脑组织磷酸化ERK1／2（pERK1／2）的表达，RT-PCR法检测c-fos mRNA的表达，免疫组织化学法检测pERK1／2和c-fos蛋白在损伤脑组织中的分布。结果 DBI后脑组织中pERK1／2表达增高，5min达峰值，并持续高水平表达至72h。c-fos与pERK1／2变化趋势相似，但峰值出现较晚。注射U0126后，pERK1／2表达受抑制，c-fos mRNA表达减少（P〈0．05），c-fos阳性细胞平均灰度值升高（P〈0．05）。结论大鼠DBI后ERK1／2通路被过度和持久激活，阻滞ERK1／2活化可以下调c-fos基因的表达。

Effect of Inhibition of ERK1/2 Cascade on c-fos Gene Expression in Diffuse Brain Injury

Objective To study the effect of U0126,a specific inhibitor of extracellular signal regulated kinase 1/2(ERK1/2) pathway,on the gene expression of c-fos in traumatic diffuse brain injury of rats.Methods Marmarou's free falling-body method was used to induce brain injury.U0126 was injected intravenously through caudal vein.The expression of phosphorylated ERK1/2(pERK1/2) and c-fos mRNA was detected by Western blot and RT-PCR respectively.Immunohistochemistry was applied to determine the regional distribution of pERK1/2 and c-fos positive cells in injured brain tissues.Results The results of Western blot revealed that the expression of pERK1/2 was significantly increased and reached peak 5 min after trauma,and kept high level for 72 h.The expression of c-fos gene had a similar tendency to pERK1/2 in temporal profiles,but presented a later peak.Treatment with U0126 effectively prevented the activation of ERK1/2 and attenuated the expression of c-fos gene(P<0.05).Conclusion ERK1/2 pathway was over-and sustained-activated in diffuse brain injury following trauma.Inhibition of this pathway by U0126 could attenuate the expression of c-fos gene.