Liu Hai-Tao, Li Fei, Wang Wen-Yong, Li Xiao-Jing, Liu Yi-Meng, Wang Rui-An, Guo Wen-Yi, Wang Hai-Chang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
Tex Heart Inst J. 2010;37(2):194-201.
Endothelial-cell function is important in the healing of damaged endothelium after percutaneous coronary artery damage. In 3 different animal models, we sought to determine whether rapamycin (sirolimus) affects the proliferation and migration of endothelial cells and endothelial progenitor cells. First, after we implanted stents in dogs, we found that re-endothelialization was impeded more by drug-eluting stents than by bare-metal stents, 30 days after percutaneous coronary intervention. Second, in vitro in rats, we found that 1-100 ng/mL of rapamycin time- and dose-dependently inhibited proliferation over 72 hr (with effects evident as early as 24 hr) and also dose-dependently induced endothelial progenitor-cell apoptosis. Finally, in vivo in rats, we observed that vascular endothelial growth factor expression was decreased after 5 days of rapamycin treatment. We conclude that rapamycin impedes re-endothelialization after drug-eluting stent implantation by inhibiting the proliferation and migration of coronary endothelial cells, inducing endothelial progenitor-cell apoptosis, and decreasing vascular endothelial growth factor expression in the circulation.
内皮细胞功能在经皮冠状动脉损伤后受损内皮的愈合过程中很重要。在3种不同的动物模型中，我们试图确定雷帕霉素（西罗莫司）是否会影响内皮细胞和内皮祖细胞的增殖与迁移。首先，在给狗植入支架后，我们发现经皮冠状动脉介入治疗30天后，药物洗脱支架比裸金属支架对再内皮化的阻碍更大。其次，在大鼠体外实验中，我们发现1 - 100 ng/mL的雷帕霉素在72小时内对增殖有时间和剂量依赖性抑制作用（早在24小时就有明显效果），并且还对内皮祖细胞凋亡有剂量依赖性诱导作用。最后，在大鼠体内实验中，我们观察到雷帕霉素治疗5天后血管内皮生长因子表达降低。我们得出结论，雷帕霉素通过抑制冠状动脉内皮细胞的增殖和迁移、诱导内皮祖细胞凋亡以及降低循环中的血管内皮生长因子表达，阻碍了药物洗脱支架植入后的再内皮化。
