摘要
目的探讨大鼠弥漫性脑损伤后磷酸化ERK1/2和基质金属蛋白酶-9(MMP-9)的变化规律及相互作用关系,从而进一步理解ERK1/2在弥漫性脑损伤中的作用及其对脑的保护机制。方法按Mamarou方法制作大鼠重型弥漫性脑损伤模型,尾静脉注射ERK通路阻滞剂U0126；Western blot法检测磷酸化ERK1/2；RT-PCR检测MMP-9 mRNA,干湿重法测脑组织含水量。结果弥漫性脑损伤后磷酸化ERK1/2表达迅速增高,持续高水平表达至72 h。MMP-9 mRNA在损伤后3 h开始上升,24 h达高峰,可维持较高水平直至7 d。注射U0126后,磷酸化ERK1/2表达明显下降(P＜0．01),MMP-9 mRNA表达亦明显下降(P＜0．05),脑组织含水量减少(P＜0．05)。结论大鼠重型弥漫性脑损伤后ERK1/2被过度激活,MMP-9 mRNA表达增高,通过阻滞ERK通路可以下调MMP-9 mRNA的表达,保护受损脑组织。
Objective To study the expressions of phosphorylated extracellular signal regulated kinases1/2 （pERK1/2） and matrix metalloproteinase-9 （MMP-9） mRNA in the brain tissues of rats with traumatic diffuse brain injury （DBI） and their changes after treatment with U0126 in order to understand the role of ERK1/2 in DBI and its potential protective mechanism for the brain. Methods The severe DBI was produced by free falling-body method in rats. U0126 was injected into caudal veins in the rats of the experimental group. The pERK1/2 was determined by Western blot analysis. MMP-9 mRNA level was determined by RT-PCR. The water content in the injured brain tissues was determined by dry-wet weight method. Results The pERK1/2 was rapidly upregulated after DBI, reached the peak at 5 minutes after DBI, and kept high level till 72 hours after DBI. Treatment with U0126, a specific inhibitor of ERK1/2 Pathway, significantly prevented the activation of ERK1/2 （P〈0.01）. The expression of MMP-9 mRNA began to increase 3 hours after DBI, peaked at 24 hours after DBI and kept high level till the 7th day after DBI. U0126 significantly reduced the MMP-9 mRNA and pERK1/2 levels, and water content in the injured brain tissue （P〈0.05）. Conclusions After severe DBI, ERK pathway was over activated and MMP-9 mRNA also significantly increased. MMP-9 levels and brain edema in the injured brain tissues can be decreased by inhibition of ERK cascades with U0126, which may probably be a new way to treat severe DBI.
出处
《中国临床神经外科杂志》
2006年第5期288-291,共4页
Chinese Journal of Clinical Neurosurgery
