Endostatin expression in neurons during the early stage of cerebral ischemia is associated with neuronal apoptotic cell death in adult hypertensive rat model of stroke
Endostatin expression in neurons during the early stage of cerebral ischemia is associated with neuronal apoptotic cell death in adult hypertensive rat model of stroke
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DOI：
10.1016/j.brainres.2009.11.033
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发表时间：
2010-01-22
期刊：
影响因子：
2.9
通讯作者：
Zeng, Jinsheng
中科院分区：
文献类型：
--
作者：
Hou, Qinghua;Ling, Li;Zeng, Jinsheng
内皮抑制素（Endostatin，ES）已被认为是一种有效的抗血管生成因子。我们在此研究了ES在缺血脑中的表达以及表达ES的细胞在成年易卒中肾血管性高血压大鼠卒中后的后果。在远端大脑中动脉闭塞（dMCAO）后立即通过腹膜内注射给予单剂量的Ca-074 ME（一种膜渗透性组织蛋白酶B（CB）特异性抑制剂）或载体，使用荧光免疫组织化学染色评估ES表达，并通过测量CB从其特异性底物释放的游离7-氨基-4-甲基香豆素（AMC）来测试CB酶活性，在dMCAO后6小时，Z-Arg-Arg-7-amido-4-methylcoumarin ES免疫反应性（IR）显著上调，并在第3天恢复到基线水平。染色实验显示大部分缺血诱导的ES阳性细胞是神经元。此外，ES用CB和切割的Caspase-3（Asp 175）共标记，而用Ca-074 ME处理减少了ES表达的上调并减弱了梗死前神经元的凋亡。我们的数据表明，在脑缺血的早期阶段，脑梗塞前神经元表达ES，并且用Ca-074 ME治疗减弱脑梗塞前神经元中的ES表达和细胞凋亡（C）2009 Elsevier B V保留所有权利
Endostatin (ES) has been recognized as a potent anti-angiogenic factor We here investigated the expression of ES in ischemic brain and the consequence of cells expressing ES after stroke in adult stroke-prone renovascular hypertensive rats A single dose of Ca-074ME, a membrane-permeable cathepsin B (CB) specific inhibitor, or vehicle was given by intraperitoneal injection immediately after distal middle cerebral artery occlusion (dMCAO), ES expression was evaluated using fluorescent immunohistochemistry staining, and CB enzyme activity was tested by measuring the free 7-amino-4-methylcoumarin (AMC) released by CB from its' specific substrate, the Z-Arg-Arg-7-amido-4-methylcoumarin ES immunoreactivity (IR) was significantly up-regulated as early as 6 h and returned to baseline level at 3 days in pen-infarct area following dMCAO Double-staining experiment revealed that the majority of ischemia-induced ES positive cells were neurons Furthermore, ES was co-labeled with CB and Cleaved Caspase-3(Asp175) whereas treatment with Ca-074ME reduced up-regulation of ES expression and attenuated apoptosis in pen-infarct neurons Collectively, our data suggest that pen-infarct neurons express ES during the early stage of cerebral ischemia and treatment with Ca-074ME attenuates ES expression and apoptosis in pen-infarct neurons (C) 2009 Elsevier B V All rights reserved