Division of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.
PLoS One. 2011 Feb 23;6(2):e17062. doi: 10.1371/journal.pone.0017062.
Reduced endothelial nitric oxide synthase (eNOS) function has been linked to secondary complications of subarachnoid hemorrhage (SAH). We previously found that there is increased eNOS function after SAH but that it is uncoupled, leading to secondary complications such as vasospasm, microthromboembolism and neuronal apoptosis. Here we test the hypothesis that recoupling eNOS with simvastatin can prevent these complications. SAH was created in mice that were treated with vehicle or simvastatin starting 2 weeks before or 30 minutes after SAH. SAH increased phosphorylated eNOS which was prevented by pre- or post-treatment with simvastatin. Simvastatin pre-treatment also prevented the increase in eNOS monomer formation that was associated with SAH, decreased superoxide anion radical production and increased NO. These changes were associated with decreased vasospasm, microthromboemboli and neuronal injury. The data suggest that simvastatin re-couples eNOS after SAH, leading to decreased secondary complications such as vasospasm, microthromboemboli and neuronal injury.
内皮型一氧化氮合酶（eNOS）功能降低与蛛网膜下腔出血（SAH）的继发性并发症有关。我们之前发现，SAH 后 eNOS 功能增加，但发生解偶联，导致血管痉挛、微血栓形成和神经元凋亡等继发性并发症。在这里，我们验证了这样一个假设，即通过辛伐他汀使 eNOS 重新偶联可以预防这些并发症。在 SAH 前 2 周或 SAH 后 30 分钟开始用载体或辛伐他汀处理小鼠，以建立 SAH。SAH 增加了磷酸化的 eNOS，而辛伐他汀的预处理或后处理可以预防这一增加。辛伐他汀预处理还可以防止与 SAH 相关的 eNOS 单体形成增加，减少超氧阴离子自由基的产生，增加一氧化氮。这些变化与血管痉挛、微血栓形成和神经元损伤减少有关。数据表明，辛伐他汀在 SAH 后使 eNOS 重新偶联，从而减少血管痉挛、微血栓形成和神经元损伤等继发性并发症。
