细胞外信号调节激酶在蛛网膜下腔出血损伤中的作用及意义

Role of extracellular signal regulated kinase after subarachnoid hemorrhage in mice

目的研究细胞外信号调节激酶(ERK)途径在蛛网膜下腔出血(SAH)脑损伤中的作用。方法ICR小鼠随机分为假手术组、模型组、U0126干预组,采用非开颅血管内穿线法制备小鼠SAH模型,给予ERK抑制剂U0126,术后行颅底检查,分别在SAH后12、24、48h 3个时相点取右侧大脑动脉标本,在光镜下观察大脑中动脉病理变化,应用免疫印迹法检测各组p-ERK1/2、caspase-8蛋白表达,TUNEL法检测大脑中动脉内皮细胞凋亡。结果随损伤时间延长,模型组小鼠p-ERK1/2、caspase-8蛋白均有不同程度增强,凋亡细胞增多。与模型组比较,U0126干预组小鼠各时相点3项指标的表达均不同程度下调。结论 ERK信号途径参与小鼠SAH病理损伤过程,并在神经细胞凋亡进程中发挥关键作用。

Objective To investigate the role of extracellular signal regulated kinase（ERK）signaling pathway after subarachnoid hemorrhage（SAH） in mice.Methods ICR mice were randomly divided into three groups：sham operation group,NS＋SAH group and U0126＋SAH group,We made a stable and reliable mice SAH model by endovascular perforation without opening cranium,and then examine the cranial base.At different time points（12h,24h and 48h） after operation,the tissues of arteriae cerebri were sampled,changes in MCA were observed with light microscopy,Western blot assay was used to examine the p-ERK1/2,caspase-8 expression,and apoptotic cell number were determined by TUNEL.Results In SAH group,the p-ERK1/2 and caspase-8 level and the number of apoptosis cells was significantly enhanced.The expression of p-ERK1/2,caspase-8 and the number of apoptosis cells were lower in the U0126 group than those in the SAH group.Conclusion The activated ERK1/2 signaling pathway plays all important role in processing of neuron cell apoptosis after SAH.