N omega-nitro-L-arginine attenuates early ischemic neuronal damage of prolonged focal cerebral ischemia and recirculation in rats.
N omega-nitro-L-arginine attenuates early ischemic neuronal damage of prolonged focal cerebral ischemia and recirculation in rats.
复制标题
N omega-硝基-L-精氨酸可减轻大鼠长期局灶性脑缺血和再循环的早期缺血性神经元损伤。
作者：
T. Matsui;T. Nagafuji;T. Mori;T. Asano
本研究旨在探讨N-奥米伽-硝基-L-精氨酸对早期缺血性神经元损伤(EIND)的影响。所有实验均在全身麻醉下进行，维持血气和体温在生理范围内。采用本实验室研制的Miniclip大脑中动脉(MCA)长时间或暂时性闭塞模型，测定每只大鼠的局部脑血流量(CBF)、相应的局部皮质比重和EIND体积。仅在局部脑血流量低于200ml100g-1min-1的脑区才出现明显的皮质水肿。大脑中动脉阻塞1、2、4h后，脑皮质水肿程度和脑内体积均呈时间依赖性增加。取出夹子总是会引起再循环。与长时间缺血4h相比，缺血1h再灌流3h可明显改善脑损伤，而缺血2h再灌流则明显加重脑组织损伤。LNA[1 mg，ip，在实验期间分两次给予]仅部分抑制脑组织一氧化氮合酶的活性，但显著改善该模型的长时间缺血和再循环的EED。上述结果提示一氧化氮在长时间缺血和再循环中的致病作用。
The present study aimed to examine the effects of N omega-nitro-L-arginine (LNA) on the early ischemic neuronal damage (EIND). All the experiments were carried out under general anesthesia, maintaining the blood gases and the body temperature within the physiological ranges. The local CBF, the topographically corresponding cortical specific gravity, and the volume of EIND were determined in each rat, which was subjected to prolonged or temporary occlusion of middle cerebral artery (MCA) using our original miniclip. Significant cortical edema developed only in the brain area where the local CBF value was below 200 ml 100 g-1 min-1. The prolonged MCA occlusion for 1, 2, and 4 h induced a time-dependent increase in the severity of cortical edema and the volume of EIND. Removal of the clip invariably induced recirculation. Compared to that induced by 4 h prolonged ischemia, the brain damage was improved by 1 h MCA occlusion followed by 3 h recirculation, whereas it was significantly worsened by 2 h ischemia followed by 2 h recirculation. While LNA [1 mg, i.p., given two times during the experiment] only partially inhibited the activity of brain nitric oxide synthase, it remarkably ameliorated EIND of both prolonged ischemia and recirculation in this model. The above findings indicate the pathogenic role of nitric oxide in prolonged ischemia as well as recirculation.