Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat
Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat
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DOI：
10.1016/j.neuroscience.2006.09.014
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发表时间：
2006-12-28
期刊：
影响因子：
3.3
通讯作者：
Zhang, J. H.
中科院分区：
文献类型：
--
作者：
Solaroglu, I.;Tsubokawa, T.;Zhang, J. H.
我们研究了粒细胞集落刺激因子（G-CSF）对神经元抗凋亡特性的分子机制，以及G-CSF是否影响大鼠局灶性脑缺血后胶质细胞的存活。通过管腔内闭塞技术使Sprague-Dawley大鼠经受短暂的大脑中动脉闭塞（MCAO）90分钟。将大鼠用单剂量的G-CSF（50 μ g/kg，s.c.）在再灌注开始时或G-CSF（50 μ g/kg体重，s.c.）在再灌注开始时开始给药，然后每天给药相同剂量，再给药2天。再灌注后24 h、72 h或2周收集脑组织，用于测定梗死体积、免疫组织化学研究和Western印迹分析磷酸化信号转导和转录激活因子3（pSTAT 3）、Pim-1、bcl-2、Bax、细胞色素c、细胞凋亡抑制蛋白2（cIAP 2）和裂解的caspase-3水平。G-CSF显著减少梗死体积，改善早期神经功能结局。G-CSF处理显著上调pSTAT 3，Pim-1，bcl-2表达，下调细胞色素c释放到胞质溶胶，Bax易位到线粒体，并在神经元中裂解caspase-3水平。STAT 3通路的激活伴随着胶质细胞中cIAP 2表达的增加。MCAO后，G-CSF治疗通过影响不同的抗凋亡途径增加神经元和神经胶质细胞的存活，这反映了该药物的多因素作用。这些变化与组织保存和行为结果的显著改善相关。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
We investigated the molecular mechanisms of the anti-apoptotic properties of granulocyte-colony stimulating factor (G-CSF) on neurons and whether G-CSF affects glial cell survival following focal cerebral ischemia in rats. Sprague-Dawley rats were subjected to a transient 90 min middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. Rats were treated with either a single dose of G-CSF (50 mu g/kg, s.c.) at the onset of reperfusion or G-CSF (50 mu g/kg body weight, s.c.) was administered starting at the onset of reperfusion and followed by the administration of the same dose per day for an additional 2 days. Brains were harvested either 24 h, 72 h or 2 weeks after reperfusion for assays of infarct volume, immunohistological studies and Western blot analysis for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), Pim-1, bcl-2, Bax, cytochrome c, cellular inhibitor of apoptosis protein 2 (cIAP2), and cleaved caspase-3 levels. G-CSF significantly reduced infarct volume and ameliorated the early neurological outcome. G-CSF treatment significantly up-regulated pSTAT3, Pim-1, bcl-2 expression, and down-regulated cytochrome c release to the cytosol, Bax translocation to the mitochondria, and cleaved caspase-3 levels in neurons. The activation of the STAT3 pathway was accompanied by increased cIAP2 expression in glial cells. After MCAO, G-CSF treatment increased both neuronal and glial survival by effecting different anti-apoptotic pathways which reflects the multifactorial actions of this drug. These changes were associated with remarkable improvement in tissue preservation and behavioral outcome. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.