CXCR4 Antagonist AMD3100 Protects Blood-Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice
CXCR4 Antagonist AMD3100 Protects Blood-Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice
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CXCR4 拮抗剂 AMD3100 保护小鼠血脑屏障完整性并减少局灶性缺血后的炎症反应
DOI：
10.1161/strokeaha.112.670299
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发表时间：
2013-01-01
期刊：
影响因子：
8.3
通讯作者：
Wang, Yongting
中科院分区：
文献类型：
--
作者：
Huang, Jun;Li, Yaning;Wang, Yongting
背景与目的：炎症反应在局灶性脑缺血后组织损伤的传播中起关键作用。CXCL12是白细胞募集的关键趋化因子。然而，CXCL12及其受体CXCR4在缺血诱导炎症反应中的作用尚不清楚。本研究使用CXCR4的药理拮抗剂AMD3100来研究CXCL12/CXCR4在急性缺血时调节炎症反应的功能。方法：成年雄性CD-1小鼠184只，采用永久性缝合性大脑中动脉闭塞术（MCAO）。MCAO后注射AMD3100 3天（1 mg/kg/天）。在MCAO后24,48和72小时检测脑含水量，梗死体积，神经学评分和髓过氧化物酶（MPO）表达和活性。采用RT-PCR和酶联免疫吸附法检测脑组织促炎细胞因子RNA和蛋白水平。结果：MCAO 3 d后，与对照组相比，amd3100治疗小鼠的神经学评分显著提高(P
Background and Purpose-Inflammatory response plays a critical role in propagating tissue damage after focal cerebral ischemia. CXCL12 is a key chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the pharmacological antagonist of CXCR4, AMD3100, to investigate the function of CXCL12/CXCR4 in regulating inflammatory response during acute ischemia.Methods-Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain water content, infarct volume, neurological score, and myeloperoxidase (MPO) expression and activity were examined at 24, 48, and 72 hours after MCAO. Proinflammatory cytokine RNA and protein levels in brain tissue were measured by RT-PCR and enzyme linked immunosorbent assay.Results-Neurological score was greatly improved in AMD3100-treated mice compared with the control mice 3 days after MCAO (P