莪术愈创木烷型倍半萜化合物调节血管内皮细胞/平滑肌细胞增殖迁移的分子机制研究

项目名称： 莪术愈创木烷型倍半萜化合物调节血管内皮细胞/平滑肌细胞增殖迁移的分子机制研究

项目编号： No.81473530

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 赵福海

作者单位： 中国中医科学院西苑医院

项目金额： 66万元

中文摘要： 莪术提取物具有抑制血管平滑肌细胞(VSMC)增殖、抑制炎症反应、促进血管内皮细胞（VETC）修复等作用。前期研究表明莪术组分（莪术愈创木烷型倍半萜化合物，ZGSC）支架在抑制血管内再狭窄、血管再内皮化方面优于雷帕霉素支架，机制涉及调节VSMC增殖周期，减轻炎症反应等方面。内皮一氧化氮合酶/小凹蛋白-1(eNOS/Cav-1)是内皮保护及再内皮化重要信号通路，莪术组分支架抑制血管内再狭窄、促进血管再内皮化的机理是否与Cav-1介导的eNOS表达增加相关，尚缺少研究。针对这一问题，本研究用离体培养大鼠VSMC及VETC模型，研究ZGSC对VSMC/VETC增殖、迁移、凋亡的影响,验证ZGSC调节VSMC增殖周期的药理效应；以cav-1静默基因和eNOS静默基因结合，观察其对内皮信号eNOS/Cav-1表达影响，阐明ZGSC抑制VSMC增殖、促进内皮化的分子机制。为其临床转化应用提供实验依据。

中文关键词： 莪术愈创木烷型倍半萜化合物；血管内皮细胞；血管平滑肌细胞；内皮型一氧化氮合酶；小凹蛋白-1

英文摘要： Zedoary essential components involve in suppressing vascular smooth muscle cell(VSMC)proliferation, facilitating vascular endothelial cell(VETC) coverage,inhibiting platelet aggregation and attenuating inflamatory recation pleiotropic pharmacological effect. Our previous study found Nano-micropore stent eluting zedoary essential components (zedoary guaiane sesquiterpenes compounds，ZGSC) was not inferior to sirolimus eluting stent on inhibition of neointima proliferation and promotion endothelial coverage.The potential mechanism concern that ZGSC regulate VSMC proliferation cycle, facilitate vascular endothelialization mediated by inflammatory factors. The eNOS/Cav-1 gene is a pivotal signal pathway on vascular endothelia protection and reendothelialization.Data is unavailable about relation of incremental expression of eNOS mediated by Cav-1 and restenosis /reendothelialization mediated by ZGSC. To verify the hypothesis, current experiments utilizing mice VETC and VSMC model in vitro to explore ZGSC action targets on VSMC cycle of proliferation, migration and apoptosis. Moreover, to probe the key mechanism of ZGSC on eNOS/Cav-1 signal pathway by Cav-1 and eNOS gene silence model in vitro utilizing aortic endothelial cell culture to elucidate the mechanism of ZGSC on vascular endothelia signal pathway and VSMC proliferation cycle.

英文关键词： zedoary guaiane sesquiterpenes compounds;vascular endothelial cell;vascular smooth muslce cell;eNOS;Cav-1