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首页> 外文期刊>Translational Stroke Research >Suppression of the Rho/Rho-Kinase Pathway and Prevention of Cerebral Vasospasm by Combination Treatment with Statin and Fasudil After Subarachnoid Hemorrhage in Rabbit
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Suppression of the Rho/Rho-Kinase Pathway and Prevention of Cerebral Vasospasm by Combination Treatment with Statin and Fasudil After Subarachnoid Hemorrhage in Rabbit

机译：蛛网膜下腔出血后他汀和法舒地尔联合治疗抑制Rho / Rho激酶途径并预防脑血管痉挛

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摘要

The Rho/Rho-kinase pathway is considered important in the pathogenesis of sustained smooth muscle cell contraction during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The aims of this study were to investigate whether combination treatment, with pitavastatin as an inhibitor of RhoA and fasudil as an inhibitor of Rho-kinase, prevents the cerebral vasospasm. SAH was simulated using the double-hemorrhage rabbit model, and pitavastatin, or fasudil, or both (combination treatment) were administrated. The basilar artery (BA) cross-sectional area only in the combination treatment group was statistically larger than in the SAH group (p < 0.05). BA Rho-kinase, as measured by ELISA, was statistically reduced only in the combination treatment group compared with the SAH group (p < 0.05). In the other two treatment groups, pitavastatin or fasudil treatment group showed larger BA cross-sectional areas and lower value for BA Rho-kinase, but there were no statistically significant differences compared with the SAH group. The expression of endothelial nitric oxide synthase (eNOS), evaluated by immunohistochemistry in the pitavastatin group and the combination group, was higher than in the SAH group. Results indicate that combination treatment could extensively prevent cerebral vasospasm due to the synergic effect of combining pitavastatin and fasudil on the Rho/Rho-kinase pathway and on eNOS.
机译：Rho / Rho激酶途径被认为在动脉瘤性蛛网膜下腔出血（SAH）后脑血管痉挛期间持续平滑肌细胞收缩的发病机理中很重要。这项研究的目的是研究用匹伐他汀作为RhoA抑制剂和法舒地尔作为Rho激酶抑制剂的联合治疗是否能预防脑血管痉挛。使用双出血兔模型模拟SAH，并给予匹伐他汀或法舒地尔或两者（联合治疗）。在统计学上，仅联合治疗组的基底动脉（BA）截面积大于SAH组（p <0.05）。通过ELISA测定的BA Rho激酶仅在联合治疗组比SAH组有统计学意义的降低（p <0.05）。在其他两个治疗组中，匹伐他汀或法舒地尔治疗组的BA横截面积较大，BA Rho激酶的值较低，但与SAH组相比无统计学差异。通过免疫组织化学评估，匹伐他汀组和联合组的内皮型一氧化氮合酶（eNOS）的表达高于SAH组。结果表明，由于匹伐他汀和法舒地尔联合使用对Rho / Rho激酶途径和eNOS具有协同作用，因此联合治疗可广泛预防脑血管痉挛。

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