摘要
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,5 min达峰值,并持续高水平表达至72 h。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。
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.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2006年第3期343-345,349,共4页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
