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目的探讨紫杉醇对兔血管内皮和平滑肌增生影响的差异及意义。方法将兔血管平滑肌细胞接种于共培养体系上室、内皮细胞接种于下室建立体外内膜修复模型,观察紫杉醇对兔血管平滑肌和内皮细胞3H-TdR掺入、细胞计数和迁移率的影响,用直线回归法计算紫杉醇对平滑肌和内皮细胞增生迁移的半数有效抑制浓度IC50。结果在1 nmol·L-1~1μmol·L-1之间,紫杉醇呈浓度依赖地抑制平滑肌细胞3H-TdR掺入、细胞计数和迁移(n=6 ,P<0 .01)。在10 nmol·L-1~1μmol·L-1之间,紫杉醇呈浓度依赖地抑制内皮细胞3H-TdR掺入、细胞计数和迁移(n=6 ,P<0 .01)。1 nmol·L-1紫杉醇对内皮细胞3H-TdR掺入和细胞计数有抑制倾向,但与对照组相比无统计学差异。而1 nmol·L-1的紫杉醇却已显著抑制内皮细胞迁移(n=6 ,P<0 .01)。紫杉醇对兔血管平滑肌细胞增生、迁移抑制的IC50分别为10 .09±0 .47、9 .16±0 .54 nmol·L-1,对内皮细胞增生、迁移抑制的IC50分别为19 .05±0 .35、5 .37±0 .51nmol·L-1。10 nmol·L-1紫杉醇作用20 min在观察时间内能持续抑制融合内皮组平滑肌增生,而对数内皮组平滑肌增殖在10 d时明显高于对照组。结论紫杉醇在抑制兔血管平滑肌细胞增生的同时也抑制内皮增生,紫杉醇干预后平滑肌细胞增生延迟与内皮细胞再生延迟密切相关。
Objective To investigate the difference and significance of paclitaxel on vascular endothelial and smooth muscle hyperplasia in rabbits. Methods Rabbit vascular smooth muscle cells were seeded on the upper chamber of co-culture system and endothelial cells were seeded into the lower chamber to establish an in vitro model of intimal repair. The effects of paclitaxel on 3H-TdR incorporation, cell counting and migration of vascular smooth muscle and endothelial cells were observed. The linear regression method was used to calculate the effective inhibitory concentration (IC50) of paclitaxel on the proliferation and migration of smooth muscle and endothelial cells. Results Paclitaxel inhibited 3H-TdR incorporation, cell counting and migration in smooth muscle cells (n = 6, P <0.01) in a concentration-dependent manner from 1 nmol·L-1 to 1 μmol·L-1. Paclitaxel inhibited 3H-TdR incorporation, cell counting and migration (n = 6, P <0.01) in a concentration-dependent manner at concentrations between 10 nmol·L-1 and 1 μmol·L-1. 1 nmol·L-1 paclitaxel inhibited 3H-TdR incorporation and cell counting in endothelial cells, but no significant difference compared with control group. Paclitaxel at a concentration of 1 nmol·L -1 significantly inhibited endothelial cell migration (n = 6, P <0.01). The IC50 of paclitaxel on the proliferation and migration of rabbit vascular smooth muscle cells were 10 .09 ± 0.47,9. 96 ± .54 nmol·L-1, respectively. The IC50 of inhibition on endothelial cell proliferation and migration were 19.05 ± 0.05, 5.37 ± 0.51nmol·L-1.10 nmol·L-1 paclitaxel for 20 min in the observation time can continue to inhibit smooth muscle cell proliferation in the fusion endothelium, while logarithmic endothelium smooth muscle cell proliferation at 10 d Obviously higher than the control group. Conclusion paclitaxel inhibits the proliferation of rabbit vascular smooth muscle cells and inhibits the proliferation of endothelial cells. The paclitaxel-induced delayed proliferation of smooth muscle cells is closely related to the delayed regeneration of endothelial cells.