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

通过对单侧和双侧蛛网膜下腔出血(SAH)模型的比较，探讨基底动脉血管痉挛时血管平滑肌细胞变性的机制。电子显微组织化学研究显示，在第二次SAH诱导后，线粒体钙超载的持续时间长于第一次SAH模型。免疫组织化学研究显示，单侧SAH模型中细胞色素c在胞浆中未检测到，而双侧SAH模型中细胞色素c在SAH后4~7d由线粒体释放到胞浆中。在单侧蛛网膜下腔出血模型中，μ-Calain在基底动脉短暂激活，而在双侧蛛网膜下腔出血模型中，μ-Calain和Caspase-3(CPP32)在4d后持续显著激活。此外，SAH模型大鼠基底动脉中促进和保护细胞色素c释放的Bclxl和Bclxs的含量在SAH后7d均明显减少，但二者的比值显著降低。提示线粒体依赖的亚致死信号可能在迟发性脑血管痉挛的发病机制中起重要作用。

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.