Compared with
paclitaxel,
sirolimus has been more used in the treatment of vascular restenosis gradually as an anti-proliferative
drug, but few basic studies have elucidated its mechanism. The anti-proliferative effects of
sirolimus or
paclitaxel have been demonstrated by numerous studies under normoxia, but few studies have been achieved focusing
hypoxia. In this study, porcine
carotid artery injury model and classical
cobalt chloride hypoxia cell model were established.
Sirolimus nanoparticles (SRM-NPs),
paclitaxel nanoparticles (PTX-NPs) and blank nanoparticles (Blank-NPs) were prepared respectively. The effect of RPM-NPs on the degree of
stenosis, proliferative index and the expression of
PCNA after 28 days of porcine
carotid artery injury model was evaluated. Compared with saline group and SRM groups, SRM-NPs group suppressed vascular
stenosis, proliferative index and the expression of
PCNA (P < 0.01 and P < 0.05). Endothelial cell (EC) and smooth muscle cell (SMC) were pre-treated with
cobaltous chloride, followed by SRM-NPs, PTX-NPs, Blank-NPs or PBS control treating, the effects on cell proliferation, HIF-1 expression and glycolysis were detected. SRM-NPs could inhibit EC and SMC proliferation under
hypoxia, while PTX-NPs couldn't (P < 0.001). Significant differences between
sirolimus and
paclitaxel NPs in anti-proliferation effect under normoxia and
hypoxia may due to the different inhibitory effects on HIF-1α expression and glycolysis. In conclusion, these results suggest that
sirolimus can inhibit the proliferation of hypoxic cells more effectively than
paclitaxel. These observations may provide a basis for understanding clinical vascular
stenosis therapeutic differences between
rapamycin and
paclitaxel.