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

脑血管痉挛时平滑肌细胞为何收缩变性？

• 批准号: 12671364
• 负责人: OHTA Shinsuke
• 金额: $ 1.41万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671364/
• 关键词: Cerebral vasopasam; Subarachnoid hemorrhage; Caspase-3; Calpain; Calcium; ミトコンドリア; caspase; チトクロームc; bcl; チトクロームC

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.

我们通过比较单蛛网膜下腔出血和双蛛网膜下腔出血（SAH）模型，分别培养了大量TUNEL阳性平滑肌细胞，阐明了基底动脉平滑肌细胞变性伴血管痉挛的机制。电子显微组织化学研究表明，在双SAH模型中，Ca^<++>在第二次SAH诱导后对线粒体的过载持续时间比第一次SAH诱导时更长。免疫组化研究表明，在单SAH模型中细胞质中未检测到细胞色素c，而在双SAH模型中，细胞色素c在初始SAH后4 ~ 7天从平滑肌细胞的线粒体中释放到细胞质中。单SAH模型基底动脉中μ-calpain在SAH诱导后短暂激活，而双SAH模型中μ-calpain和caspase-3 （CPP32）在4天后显著持续激活。此外，虽然大鼠SAH模型在SAH后7天基底动脉中分别具有促进和保护细胞色素c释放作用的Bcl-xl和Bcl-xs的数量减少，但Bcl-xs和Bcl-xl的比值明显降低。这些结果提示线粒体依赖性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。

项目成果

Haruhisa Ichikawa, Shiro Ohue, Kanehisa Kohno, Shinsuke Ohta, Yoshiaki Kumon, Saburo Sakaki: "Role of Caspase-3 in the parhogenesis of cerebral vasospasm"Cerebral Vasospasm. 15. 222-225 (2000)

Haruhisa Ichikawa、Shiro Ohue、Kanehisa Kohno、Shinsuke Ohta、Yoshiaki Kumon、Saburo Sakaki：“Caspase-3 在脑血管痉挛发病中的作用”脑血管痉挛。

市川晴久, 大田信介: "Caspase-3の脳血管攣縮の果たす役割"脳血管攣縮. 15. 222-225 (2000)

Haruhisa Ichikawa、Shinsuke Ota：“Caspase-3 在脑血管痉挛中的作用”Cerebral Vasospasm 15. 222-225 (2000)。

市川晴久, 大田信介: "Caspase-3の脳血管攣縮に果たす役割"脳血管攣縮. 15. 222-225 (2000)

Haruhisa Ichikawa、Shinsuke Ota：“Caspase-3 在脑血管痉挛中的作用”Cerebral Vasospasm 15. 222-225 (2000)。

市川晴久,大田信介: "Caspase-3(CPP32)の脳血管攣縮に果たす役割"脳血管攣縮. 15. 222-225 (2000)

Haruhisa Ichikawa、Shinsuke Ota：“Caspase-3 (CPP32) 在脑血管痉挛中的作用”Cerebral Vasospasm 15. 222-225 (2000)。