ERK信号传导调节脑缺血再灌注中脑源性神经营养因子介导的神经保护作用

目的研究大脑缺血再灌注中脑源性神经营养因子(BPNF)神经保护效应的机制以及细胞外调节激酶信号通路在其中的作用。方法 SD大鼠被随机分为A、B、C三组,每组6只,所有的大鼠均经历大脑中动脉阻断诱发的脑局灶性缺血再灌注过程,此过程持续45 min。B组给予BDNF以产生神经保护,C组采用选择性Raf-1信号分子抑制剂Bay 43-9006抑制细胞外调节激酶信号通路。脑损伤用甲酚紫染色加图像分析评估,细胞外调节激酶1和2的磷酸化水平采用免疫印迹杂交测定。结果经过缺血再灌注过程,额叶脑组织的损伤比例为(16.48±5.72)%;在使用BD-NF预处理的情况下,脑组织损伤比例显著降低至(6.32±3.08)%(P=0.039)。使用Raf-1抑制剂之后,细胞外调节激酶的磷酸化水平显著降低,包括细胞外调节激酶1(P=0.0084)和细胞外调节激酶2(P=0.029)。与此同时,BDNF的神经保护效应明显减弱,与对照相比没有显著差异。结论在大鼠脑缺血再灌注中,BDNF可以抵抗损伤,细胞外调节激酶信号通路是BDNF这种抗损伤效应的关键信号调节通路。

ERK signaling pathway regulates BDNF mediated neuroprotection in cerebral ischemia-reperfusion

Objective To study the underlying mechanisms of the neuroprotective effects of brain-derived neurotrophic factor(BDNF) and the involvement of extracellular signal-regulated kinase(ERK) signaling cascade in cerebral ischemia-reperfusion.Methods Sprague-Dawley rats were categorized into groups A,B and C randomly with each group containing 6 rats.All rats were subjected to a focal ischemia-reperfusion(IR) procedure,which was achieved through middle cerebral artery occlusion(MCAO),for 45 min,BDNF was administered for neuroprotection in group B and Bay 43-9006,a selective Raf-1 inhibitor,was provided in group C for inhibiting ERK signaling cascade.Brain lesion was surveyed with cresyl violet staining plus image analysis.ERK1/2 phosphorylation levels were evaluated through immunoblotting.Results After the IR cycle,16.48%±5.72% of brain tissue loss was observed at the ipsilateral side of the frontal cortex.With pretreatment of BDNF,the lesioned area was significantly decreased to 6.32%±3.08%(P=0.039).When the signaling molecule Raf-1 was blocked,significantly down-regulated phosphorylation levels of both ERK1(P=0.0084) and ERK2(P=0.029) were detected.Meanwhile,the protective effects of BDNF were obviously attenuated,showing no significant difference comparing with the non-treated controls.Conclusions BDNF acts against brain damage in rat cerebral ischemia-reperfusion.ERK signaling pathway is a major signal transduction cascade that regulates the neuroprotection effects of BDNF.