【摘要】 目的　研究细胞外信号调节激酶 (ERKs)在脑缺血中的作用以及U0 12 6对缺血脑组织保护作用的机制。方法　线栓法制作小鼠大脑中动脉栓塞 (MCAO)模型 ,颈内静脉注射U0 12 6 ;Westernblot法和免疫组化法检测 pMEK、pERK1/2和 pElk 1;核糖核酸酶保护测定法检测IL 1βmRNA含量。 结果　注射U0 12 6后的MCAO小鼠 pMEK活性降低 ,其降低幅度与U0 12 6有剂量依赖的关系 ,并在缺血前给药有效 ;U0 12 6注射后pERK1/2和 pElk 1也表现出相似的下降变化。小鼠MCAO后 1到 2hIL 1βmRNA水平上升 ;而注射U0 12 6后IL 1βmRNA在MCAO后 1至 4h内下降。 结论　ERK在小鼠脑缺血中发挥重要作用。静脉注射MEK抑制剂U0 12 6可阻断脑缺血引起的pMEK、pERK1/2和 pElk 1的活性增加。U0 12 6通过阻断ERK通路进而降低IL 1βmRNA而对缺血脑组织产生保护作用更多还原

【Abstract】 Purpose To study the role of extracellular signal regulated kinases (ERKs) in cerebral ischemia and the mechanism of protective effects of U0126 on ischemic brain. Methods Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen.U0126 was injected intravenously through the internal jugular vein.Phosphorylated MEK (pMEK),phosphorylated ERK1/2(pERK1/2),and phosphorylated Elk-1(pElk-1) was determined by Western blot analysis or immunohistochemistry.Interleukin (IL)-1β mRNA level was measured by ribonuclease protection assay. Results pMEK was reduced in ischemic mice after U0126 injection.The reduction was dose dependent and treatment time related.pERK1/2 and pElk-1 were also reduced in a similar pattern.IL-1β mRNA increased during 1 to 2 h of MCAO.After injection of U0126,it was down-regulated during 1 to 4 h of MCAO. Conclusions ERK cascade plays a critical role in cerebral ischemia.The protective effect of U0126 against ischemic injury is probably achieved by reduction of IL-1β mRNA via the inhibition of ERK pathway.更多还原