Neuroprotective effect of ligustilide against ischaemia-reperfusion injury via up-regulation of erythropoietin and down-regulation of RTP801
Neuroprotective effect of ligustilide against ischaemia-reperfusion injury via up-regulation of erythropoietin and down-regulation of RTP801
复制标题
藁本内酯通过上调促红细胞生成素和下调RTP801对缺血再灌注损伤的神经保护作用
DOI：
10.1111/j.1476-5381.2011.01337.x
复制
发表时间：
2011-09-01
影响因子：
7.3
通讯作者：
Ke, Ya
中科院分区：
文献类型：
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作者：
Wu, Xiao-mei;Qian, Zhong-ming;Ke, Ya
背景与研究进展当归中主要的亲脂性成分当归内酯有保护脑缺血损伤的作用。然而，其机制尚不清楚。在这里，我们研究了促红细胞生成素（EPO）和应激诱导蛋白RTP 801的作用，在神经保护提供的藁本内酯对缺血再灌注（I/R）损伤brain.Experimental APPROACHTThe的疗效藁本内酯对I/R损伤的神经功能缺损，梗死体积和细胞活力进行了评估，使用大脑中动脉闭塞模型在大鼠体内和大鼠体外培养的神经元。EPO和RTP 801通过Western印迹分析。结果表明，川芎嗪可明显降低I/R大鼠神经功能缺损评分、梗死体积、RTP 801的表达，增加EPO的转录，提高I/R神经元的存活率和EPO水平，减少LDH的释放和RTP 801的表达。此外，藁本内酯增加ERK磷酸化（p-ERK）。PD 98059可阻断藁本内酯对p-ERK、细胞活力和EPO的作用，而LY 294002和SB 203580则不能阻断藁本内酯对p-ERK、细胞活力和EPO的作用。此外，用RTP 801质粒转染SH-SY 5 Y细胞可增加RTP 801和LDH的释放，而藁本内酯可抑制转染对RTP 801表达的影响，并增加细胞活力。结论与意义藁本内酯通过ERK信号通路促进EPO的转录和抑制RTP 801的表达，对I/R损伤具有神经保护作用。这种化合物可以开发成预防和治疗缺血性疾病的治疗剂。
BACKGROUND AND PURPOSELigustilide, the main lipophilic component of Danggui, has been reported to protect the brain against ischaemic injury. However, the mechanisms are unknown. Here, we investigated the roles of erythropoietin (EPO) and the stress-induced protein RTP801 in neuroprotection provided by ligustilide against ischaemia-reperfusion (I/R) damage to the brain.EXPERIMENTAL APPROACHThe efficacy of ligustilide against I/R damage was assessed by neurological deficit, infarct volume and cell viability, using the middle cerebral artery occlusion model in rats in vivo and rat cultured neurons in vitro. EPO and RTP801 were analysed by Western blot. Over-expression of RTP801 was achieved by transfection of an expression plasmid.KEY RESULTSLigustilide decreased the neurological deficit score, infarct volume and RTP801 expression and increased EPO transcription in I/R rats, and increased cell viability and EPO and decreased LDH release and RTP801 in I/R neurons. Also, ligustilide increased ERK phosphorylation (p-ERK). The positive effects of ligustilide on p-ERK, cell viability and EPO were blocked by PD98059, but not LY294002 and SB203580. In addition, transfection of SH-SY5Y cells with RTP801 plasmid increased RTP801 and LDH release, while ligustilide inhibited the effects of transfection on RTP801 expression and also increased cell viability.CONCLUSION AND IMPLICATIONSLigustilide exerts neuroprotective effects against I/R injury by promoting EPO transcription via an ERK signalling pathway and inhibiting RTP801 expression, This compound could be developed into a therapeutic agent to prevent and treat ischaemic disorders.