阿魏酸钠通过MEK/ERK/P90RSK信号通路减轻MCAO大鼠缺血后脑损伤效果分析

刘俊杰李建民赵雅宁徐继伟

(华北理工大学河北唐山063000)

[摘要]①目的观察阿魏酸钠(SF)对脑缺血的防治作用，分析其可能的保护机制。②方法采用线栓法阻塞大鼠大脑中动脉的方法制造大脑中动脉闭塞(MCAO)动物模型，随机分为假手术组、MCAO组、SF+假手术、SF+MCAO组，于造模前1h经尾静脉给予SF 100mg/kg和等剂量的生理盐水，24h后断头取脑，原位缺口末端标记法(TUNLE)检测凋亡神经细胞。Western bolt检测Raf-MEK-ERK通路及其下游的P90RSK、Bad蛋白磷酸化水平。③结果与模型组相比，SF干预组梗死灶的面积明显减小(P<0.05)，且凋亡细胞数量减少，MCAO组磷酸化的Raf-1、MEK1/2、ERK1/2、P90RSK、Bad较假手术组明显减少(P<0.05)，SF干预组磷酸化的Raf-1、MEK1/2、ERK1/2P90RSK、Bad较MCAO组均显著增加(P<0.05)。④结论SF可能通过MEK-ERK-P90RSK-Bad信号通路抑制MCAO后的神经元凋亡。

[关键词]脑缺血阿魏酸钠MAPKERK

[中图分类号]R 74[文献标识码]A

【基金项目】河北省科技支撑课题(编号：20276112D)；河北省教育厅自然

【作者简介】刘俊杰(1990-)，男，在读硕士研究生，医师。研究方向：脑损伤与脑保护研究。

【通讯作者】李建民。

Ferulic acid attenuates down-regulation of MEK/ERK/P90RSK signaling pathway in focal cerebral ischemic injuryLIUJunjie,LIJianmin,ZHAOYaning,etal(NorthChinaUniversityofScienceandTechnology,Tangshan063000,China)

ABSTRACT[]ObjectiveFerulic acid provides neuroprotective effects against a middle cerebral artery occlusion (MCAO)-induced cerebral ischemia.Mitogen-activated protein kinases can regulate extensive intracellular processes including cell differentiation,growth,and death.This study further investigated whether ferulic acid modulates a protective mechanism through the activation of Raf-MEK-ERK and its downstream targets,including 90 ribosomal S6 kinase (p90RSK) and Bad during cerebral ischemic injury.MethodsMale Sprague-Dawley rats were treated with ferulic acid (100 mg/kg) or vehicle befor the onset of MCAO and brain tissues were collected 24 h after MCAO.ResultsThese results indicated that ferulic acid decreases the volume of the infarct area and the number of cells positive in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Although MCAO injury induces a decrease in the phosphorylation of Raf-1,MEK1/2,and ERK1/2,ferulic acid treatment prevents the injury-induced decrease in these phosphorylation levels.Ferulic acid also attenuates the injury-induced decrease in p90RSK and Bad phosphorylation levels.ConclusionThese findings suggest that ferulic acid prevents MCAO-induced neuronal cell death and that the MEK-ERK-p90RSK-Bad signaling pathway is involved in these neuroprotective effects.

[KEYWORDS]Brain ischemia.Ferulic acid.MAPK.ERK

脑缺血加之氧化应激和能量代谢紊乱会导致严重的脑功能受损[1]。多酚类，如阿魏酸钠(sodium ferulate,SF)，又名当归素，主要存在于植物中，在细胞的生长、繁殖过程中起着重要的作用[2]。研究已经证实，SF还可以对阿尔兹海默病、脑卒中等神经系统疾病起到保护作用，其可通过抗氧化作用及抑制神经细胞凋亡从而减轻脑缺血后的损伤[3]。笔者前期研究报道SF可通过激活Akt信号通路发挥神经保护作用。

促分裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)属于丝/苏蛋白激酶家族，P44/P42 MAPK(ERK1/2)信号通路是沟通细胞内外信号的重要通路，比如生长因子、细胞分裂素信号的传递[4]。已有研究报道SF和ERK信号通路存在一定关系，SF可通过激活Akt和ERK信号通路来阻止由于辐射导致的氧化应激造成的细胞凋亡。……