雷帕霉素和紫杉醇对血管内皮细胞的增生抑制作用及细胞毒性的比较

目的比较雷帕霉素和紫杉醇对血管内皮细胞增生的抑制作用及细胞毒性作用。方法应用不同浓度的雷帕霉素和紫杉醇处理原代培养的家猪主动脉内皮细胞,使用5′-溴-2′-脱氧尿嘧啶核苷酸(BrdU)掺入法测定内皮细胞增生程度,利用CytoTox-One方法测定内皮细胞活力以反映药物的细胞毒性作用。结果极低浓度时,雷帕霉素和紫杉醇即能够显著抑制内皮细胞的增生而不伴有明显的毒性作用,雷帕霉素的抑制增生作用更强;高浓度时,二种药物几乎完全抑制内皮细胞的增生并伴有较强的毒性作用,紫杉醇的毒性作用更显著。结论雷帕霉素和紫杉醇在高浓度时均明显抑制内皮细胞的损伤后修复,紫杉醇的抑制作用尤为明显。而极低浓度的雷帕霉素仍可能会延迟血管损伤后再内皮化。

Comparison between the Inhibitory and Cytotoxic Effects of Rapamycin and Paclitaxel on Endothelial Cell Proliferation

Objective To compare the inhibitory effects of rapamycin and paclitaxel on endothelial cells'(ECs)proliferation and their cytotoxicity.Methods The primary cultured porcine aortic ECs were treated with rapamycin and paclitaxel.The cell proliferation and cell viability were assessed by BrdU incorporation and CytoTox-One method,respectively.Results Both rapamycin and paclitaxel at very low concentrations inhibited the ECs' proliferation without obvious cytotoxic effects and rapamycin showed stronger inhibitory effect.At high con-centrations,both drugs nearly inhibited the ECs' proliferation completely,accompanied by severe cytotoxic effect,which was more significant for paclitaxel.Conclusion Both rapamycin and paclitaxel,especially paclitaxel,significantly inhibit endothelial repairing at high concentra-tion.Rapamycin may delay endothelial recovery after injury even at a very low concentration.