Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells
Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells
复制标题
姜黄素减轻雷帕霉素诱导的血管内皮细胞损伤
DOI：
10.1097/fjc.0000000000000285
复制
发表时间：
2015-10-01
影响因子：
3
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Guo, Ning;Chen, Fangyuan;Zhang, Yong
药物洗脱支架（DES）虽然有效地提高了经皮冠状动脉介入治疗的临床疗效，但DES植入后也存在晚期支架内血栓形成和支架内再狭窄的高风险。抗平滑肌增殖药物如雷帕霉素、涂层支架等不仅能抑制血管平滑肌细胞的生长，而且能抑制血管内皮细胞，延缓再内皮化。因此，开发一种理想的药物来保护血管内皮细胞免受雷帕霉素洗脱支架的影响对于下一代DES具有重要意义。在这项研究中，我们证明，雷帕霉素显着抑制大鼠主动脉内皮细胞的生长在体外的剂量和时间依赖性的方式。雷帕霉素处理后，大鼠主动脉内皮细胞凋亡增加，迁移减少。令人惊讶的是，用姜黄的活性成分姜黄素治疗，显着逆转了雷帕霉素的这些不利影响。此外，姜黄素增加血管一氧化氮合酶（eNOS）的表达，这是雷帕霉素减少。此外，caveolin-1，eNOS的抑制剂，减少姜黄素。通过小干扰RNA敲低eNOS可显著消除姜黄素的保护作用。总之，我们的研究结果表明，姜黄素拮抗雷帕霉素对主动脉内皮细胞在体外通过上调eNOS的不利影响。因此，姜黄素是一种很有前途的联合药物，用于挽救DES诱导的再内皮化延迟。
Although drug-eluting stents (DES) effectively improve the clinical efficacy of percutaneous coronary intervention, a high risk of late stent thrombosis and in-stent restenosis also exists after DES implantation. Anti-smooth muscle proliferation drugs, such as rapamycin, coating stents, not only inhibit the growth of vascular smooth muscle cells but also inhibit vascular endothelial cells and delay the reendothelialization. Therefore, the development of an ideal agent that protects vascular endothelial cells from rapamycin-eluting stents is of great importance for the next generation of DES. In this study, we demonstrated that rapamycin significantly inhibited the growth of rat aortic endothelial cells in both dose- and time-dependent manner in vitro. Cell apoptosis was increased and migration was decreased by rapamycin treatments in rat aortic endothelial cells in vitro. Surprisingly, treatment with curcumin, an active ingredient of turmeric, significantly reversed these detrimental effects of rapamycin. Moreover, curcumin increased the expression of vascular nitric oxide synthases (eNOS), which was decreased by rapamycin. Furthermore, caveolin-1, the inhibitor of eNOS, was decreased by curcumin. Knockdown of eNOS by small interfering RNA significantly abrogated the protective effects of curcumin. Taken together, our results suggest that curcumin antagonizes the detrimental effect of rapamycin on aortic endothelial cells in vitro through upregulating eNOS. Therefore, curcumin is a promising combined agent for the rescue of DES-induced reendothelialization delay.