Ischemic Preconditioning Reduces Neurovascular Damage After Hypoxia-Ischemia Via the Cellular Inhibitor of Apoptosis 1 in Neonatal Brain
Ischemic Preconditioning Reduces Neurovascular Damage After Hypoxia-Ischemia Via the Cellular Inhibitor of Apoptosis 1 in Neonatal Brain
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DOI：
10.1161/strokeaha.112.677617
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发表时间：
2013-01-01
期刊：
影响因子：
8.3
通讯作者：
Huang, Chao-Ching
中科院分区：
文献类型：
--
作者：
Lin, Wan-Ying;Chang, Ying-Chao;Huang, Chao-Ching
背景和目的-神经血管单位是新生儿脑缺氧缺血（HI）损伤的主要靶点。虽然神经元是缺血预处理（IP）的细胞靶点，但血管耐受也在很大程度上起到保护作用。神经和血管在发育过程中相互交流并使用共同的信号。细胞凋亡抑制因子1（Cellular inhibitor of apoptosis 1，cIAP 1）是一种重要的细胞凋亡抑制因子。本研究假设，cIAP 1是一个共享的分子IP介导的神经血管保护对HI在新生儿brain. Methods体内IP诱导2小时可逆闭塞右颈动脉24小时前HI产后7天在大鼠幼崽。在体外建立了SH-SY 5 Y神经元细胞和人微血管内皮细胞-1血管内皮细胞的氧糖剥夺（OGD）预处理。cIAP 1表达抑制cIAP 1小干扰RNA在体内或慢病毒介导的短发夹RNA在体外，或被上调的慢病毒表达system.Results-IP减少细胞凋亡，选择性增加cIAP 1在神经元和血管内皮细胞，并提供长期的神经保护对HI。cIAP 1小干扰RNA的脑室内递送显著减弱IP介导的cIAP 1上调和体内神经保护作用。在体外，OGD预处理诱导cIAP 1和保护对OGD细胞死亡的SH-SY 5 Y神经元和人微血管内皮细胞-1。慢病毒介导的短发夹RNA敲低cIAP 1降低了SH-SY 5 Y和人微血管内皮细胞-1的OGD预处理的保护作用，而慢病毒过表达cIAP 1则保护这些细胞免受OGD的影响。（中风。2013;44：162-169）。
Background and Purpose-The neurovascular unit is a major target of hypoxia-ischemia (HI) injury in the neonatal brain. Although neurons are the cellular target of ischemic preconditioning (IP), vessel tolerance also contributes greatly to protection. Nerves and vessels cross-talk and use common signals during development. Cellular inhibitor of apoptosis 1 (cIAP1) is an important regulator that inhibits apoptosis. This study hypothesized that cIAP1 is a shared molecule underlying IP-mediated neurovascular protection against HI in the neonatal brain.Methods-In vivo IP was induced by 2-hour reversible occlusion of right carotid artery 24 hours before HI on postpartum day 7 in rat pups. In vitro oxygen-glucose deprivation (OGD) preconditioning was established in SH-SY5Y neuronal cells and in human microvascular endothelial cell-1 vascular endothelial cells. cIAP1 expression was inhibited by cIAP1 small interfering RNA in vivo or by lentivirus-mediated short hairpin RNA in vitro, or was upregulated by the lentiviral expression system.Results-IP reduced apoptosis, selectively increased cIAP1 in neurons and vascular endothelial cells, and provided long-term neuroprotection against HI. Intracerebroventricular delivery of cIAP1 small interfering RNA significantly attenuated IP-mediated cIAP1 upregulation and neuroprotection in vivo. In vitro, OGD preconditioning induced cIAP1 and protected against OGD cell death in SH-SY5Y neuronal and human microvascular endothelial cells-1. Knockdown of cIAP1 by lentivirus-mediated short hairpin RNA decreased the protective effect of OGD preconditioning in SH-SY5Y and human microvascular endothelial cell-1, whereas overexpression of cIAP1 by lentivirus protected against OGD in these cells.Conclusions-cIAP1 is a shared molecule underlying IP-induced protection in neurons and vascular endothelial cells against HI in the neonatal brain. (Stroke. 2013;44:162-169.)