Nien9C oxiok in vasospasm folloroing experimenibl subamchnoid hemo rrhege

本研究的目的是利用过表达人Cu-Zu SOD的转基因小鼠研究超氧化物歧化酶（SOD）是否抑制蛛网膜下腔出血（SAH）后实验性血管痉挛。该转基因小鼠是将人CuZn-SOD基因插入MCH （IRC）小鼠体内产生的，其SOD活性是非转基因小鼠的3倍。实验性SAH是通过从颈内动脉插入尼龙缝线穿孔大脑前动脉而产生的。小鼠分别于SAH后4小时、1天、3天、7天和14天从升主动脉灌注10%福尔马林溶液，然后再灌注碳凝胶溶液。在相差显微镜下测量大脑中动脉近端直径。sod转基因小鼠SAH后3天存活率约为70%，与非转基因小鼠无统计学差异。非转基因无SAH小鼠的MCA直径为138.5(]SY.+- . [)14.5mum（控制值，平均值（]SY.+- . [）SD,n=12）。非转基因小鼠在SAH发生后4小时、1天、7天、14天的MCA直径与对照组比较无明显变化，仅在SAH发生后3天就显著降低至110.5(]SY.+- . [)20.5mum （n=16, p<0.01）。SAH后3 d， sod转基因小鼠的MCA直径大于非转基因小鼠，差异有统计学意义(127.9(]SY.+- . [)20.2mum, n=20；p < 0.05)。这些结果提示CuZn-SOD可以减轻SAH引起的血管痉挛，血管痉挛的机制可能与超氧阴离子自由基反应有关。

The purpose of the present study is to examine whether superoxide dismutase (SOD) suppresses experimental vasospasm following subarachnoid hemorrhage (SAH) using transgenic mice overexpressing human Cu-Zu SOD.This transgenic mouse was produced by insertion of human CuZn-SOD gene to the MCH (IRC) mouse, and has three times of SOD activity compared with non-transgenic mouse. The experimental SAH was produced by perforation of the anterior cerebral artery with a nylon suture inserted from the internal carotid artery. The mice were perfused from the ascending aorta with 10% formalin solution followed by carbon gel solution 4 hours, 1 day, 3 days, 7 days, and 14 days after the SAH.The diameter of the proximal middle cerebral artery (MCA) was measured under phase-contrast microscope. The survival rate of the SOD-transgenic mice 3 days after SAH,approximately 70%, was not statistically different from that of non-transgenic mice. The MCA diameter of non-transgenic mice without SAH was 138.5(]SY.+-。[)14.5mum(control value, mean(]SY.+-。[)SD,n=12). The MCA diameter of non-transgenic mice did not change compared with the control values 4 hours, 1 day, 7 days, and 14 days after the SAH,and significantly decreased to 110.5(]SY.+-。[)20.5mum (n=16, p<0.01) only 3 days after the SAH.Three days after the SAH,the MCA diameter of the SOD-transgenic mice was larger than that of the non-transgenic mice with statistical significance (127.9(]SY.+-。[)20.2mum, n=20 ; p<0.05). These results suggest that CuZn-SOD can mitigate vasospasm caused by SAH and that the mechanism underlying vasospasm includes free radical reactions associated with superoxide anion.