Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms
Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms
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DOI：
10.1161/01.str.0000102556.55600.3b
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发表时间：
2003-12-01
期刊：
影响因子：
8.3
通讯作者：
Hashimoto, N
中科院分区：
文献类型：
--
作者：
Sadamasa, N;Nozaki, K;Hashimoto, N
背景和目的：脑动脉瘤破裂是蛛网膜下腔出血的主要原因，但其发生机制尚不清楚。诱导型一氧化氮合酶（Inducible nitric oxide synthase，iNOS）在人和大鼠脑动脉瘤中均有表达，氨基胍是一种选择性的iNOS抑制剂，可减少大鼠脑动脉瘤的数量。在这项研究中，我们应用我们的新的小鼠脑动脉瘤模型的iNOS基因敲除小鼠和观察实验性脑动脉瘤在这些动物中，以阐明在脑动脉瘤形成的过程中的作用，iNOS的8个C57/B16小鼠和16个iNOS基因敲除小鼠接受了脑动脉瘤诱导程序。手术后4个月，小鼠被杀死，他们的脑动脉被解剖，大脑前动脉/嗅动脉分叉的区域进行了组织学和免疫组织化学检查。结果-iNOS+/+和iNOS-/-小鼠之间的脑动脉瘤的发病率没有显着差异。然而，先进的脑动脉瘤的大小和凋亡的平滑肌细胞的数量在iNOS+/+小鼠比在iNOS-/- mice. Conclusions诱导型NOS是不必要的启动脑动脉瘤。然而，这项研究的结果表明，iNOS的调节可能在预防脑动脉瘤的进展中具有治疗潜力。
Background and Purpose-The rupture of a cerebral aneurysm is a major cause of subarachnoid hemorrhage, but the mechanism of its development remains unclear. Inducible nitric oxide synthase (iNOS) is expressed in human and rat cerebral aneurysms, and aminoguanidine, a relatively selective inhibitor of iNOS, can decrease the number of the aneurysms in rats. In this study we applied our new mouse model of cerebral aneurysms to the iNOS gene knockout mice and observed experimental cerebral aneurysms in these animals to elucidate the role of iNOS in the process of cerebral aneurysm formation.Methods-Eight C57/B16 mice and 16 iNOS knockout mice received a cerebral aneurysm induction procedure. Four months after the operation, the mice were killed, their cerebral arteries were dissected, and the region of the bifurcation of the anterior cerebral artery/olfactory artery was examined histologically and immunohistochemically.Results-No significant difference was seen in the incidence of cerebral aneurysms between iNOS+/+ and iNOS-/- mice. However, the size of advanced cerebral aneurysms and the number of apoptotic smooth muscle cells were significantly greater in iNOS+/+ mice than in iNOS-/- mice.Conclusions-Inducible NOS is not necessary for the initiation of cerebral aneurysm. However, the results of this study suggest that regulation of iNOS may have therapeutic potential in the prevention of the progression of cerebral aneurysms.