Atochin Dmitriy N, Clark Jeffrey, Demchenko Ivan T, Moskowitz Michael A, Huang Paul L
Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown, MA 02129, USA.
Stroke. 2003 May;34(5):1299-303. doi: 10.1161/01.STR.0000066870.70976.57. Epub 2003 Apr 3.
The purpose of this study was to test the hypothesis that nitric oxide is required for preconditioning in an intact animal model of focal ischemia using neuronal and endothelial nitric oxide synthase (nNOS and eNOS) knockout mice.
Cerebral blood flow was measured in wild-type, nNOS knockout, and eNOS knockout mice by hydrogen clearance (absolute) and laser Doppler flowmetry (relative). Mice were preconditioned by three 5-minute episodes of transient middle cerebral artery occlusion (MCAO) and subjected to permanent MCAO. Neurological deficit and infarct size were determined 24 hours later.
Although wild-type mice showed protection from ischemic preconditioning, neither eNOS nor nNOS knockout mice showed protection. Laser Doppler measurements indicated that the relative blood flow decreases in core ischemic areas were the same in all groups.
Neither eNOS nor nNOS knockout mice show protection from rapid ischemic preconditioning, suggesting that nitric oxide may play a role in the molecular mechanisms of protection.
本研究的目的是使用神经元型和内皮型一氧化氮合酶（nNOS和eNOS）基因敲除小鼠，在局灶性缺血的完整动物模型中检验一氧化氮是预处理所必需的这一假设。
通过氢清除法（绝对值）和激光多普勒血流仪（相对值）测量野生型、nNOS基因敲除和eNOS基因敲除小鼠的脑血流量。小鼠通过三次5分钟的短暂大脑中动脉闭塞（MCAO）进行预处理，然后接受永久性MCAO。24小时后测定神经功能缺损和梗死面积。
尽管野生型小鼠表现出对缺血预处理的保护作用，但eNOS和nNOS基因敲除小鼠均未表现出保护作用。激光多普勒测量表明，所有组核心缺血区域的相对血流量下降情况相同。
eNOS和nNOS基因敲除小鼠均未表现出对快速缺血预处理的保护作用，这表明一氧化氮可能在保护的分子机制中起作用。
