Why is the smooth muscle cell contracted with degeneration in cerebral vasospasm?

我们通过比较单次和双次蛛网膜下腔出血（SAH）模型，阐明了血管痉挛时基底动脉平滑肌细胞变性的机制，在该模型中分别出现了大量TUNEL阳性平滑肌细胞和非TUNEL阳性平滑肌细胞。电镜组化结果显示，在双SAH模型中，第二次SAH后线粒体Ca^++>超载持续时间较第一次长。免疫组化研究显示，虽然细胞色素c在单SAH模型中的胞质溶胶中未检测到，但在双SAH模型中，细胞色素c在初始SAH后4至7天从平滑肌细胞的线粒体释放到胞质溶胶中。在单SAH模型中，基底动脉μ-calpain在诱导SAH后即被短暂激活，而在双SAH模型中，μ-calpain和caspase-3（CPP 32）在4天后被显著且持续激活。此外，尽管在SAH模型中，在SAH后7天基底动脉中分别促进和保护细胞色素c释放的Bcl-xl和Bcl-xs的量均减少，但Bcl-xs和Bcl-xl之间的比率显著降低。提示线粒体依赖性亚致死信号在迟发性脑血管痉挛的发病机制中可能起重要作用。

We elucidated the mechanism of smooth muscle cell degeneration in the basilar arteries with vasospasm by comparing the single- and the double-subarachnoid hemorrhage (SAH) models in which no-arid massive TUNEL positive smooth muscle cells were developed, respectively. Electron microhistochemical study showed that Ca^<++> overloading to the mitochondria was sustained longer after the second SAH induction than the first one in the double-SAH model. Immunohistochemical study showed that while cytochrome c was not detected in the cytosol in the single-SAH model, cytochrome c was released to the cytosol from mitochondria in the smooth muscle cells from 4 to 7 days after the initial SAH in the double-SAH model. Though μ-calpain was transiently activated just after SAH induction in the basilar arteries of the single-SAH model, μ-calpain and caspase-3 (CPP32) was significantly and continuously activated after 4 days in the double-SAH model. In addition, although both amount of Bcl-xl and Bcl-xs which promotes and protects the release of cytochrome c, respectively, was decreased in the basilar arteries 7 days after SAH in the rat SAH model, the ratio between Bcl-xs and Bcl-xl was significantly reduced. These results suggested that the mitochondria dependent sublethal signal may play a significant role in the pathogenesis of the delayed cerebral vasospasm.