全反式维甲酸对人视网膜色素上皮细胞增生的抑制作用

Inhibitory effect of all-trans-retinoic acid on proliferation of human retinal pigment epithelial cells in vitro

目的:研究全反式维甲酸(ATRA)对体外培养人视网膜色素上皮(RPE)细胞增生的抑制作用及机制。方法:采用传代培养的人RPE细胞,分成不同浓度(10-9、10-8、10-7、10-6和10-5mol.L-1的ATRA)和不同时间点(6、12、24、48、72和96h)给药组,通过活细胞计数法、MTT比色法和流式细胞术分别检测ATRA对人RPE细胞增生的影响。结果:ATRA给药组细胞生存率低于非给药组(P<0.01)。细胞增生的抑制率与药物剂量及时间呈正相关(r1=0.9926,P<0.05;r2=0.9647,P<0.05)。与非给药组比较,ATRA给药组RPE细胞周期中G1期细胞增加(P<0.05),而G0/G1期细胞数明显减少(P<0.05)。结论:ATRA可能通过阻滞人RPE细胞周期对RPE细胞增生具有剂量依赖和时间依赖的抑制作用。

Objective To investigate the effects of all trans retinoic acid （ATRA） on proliferation of cultured human retinal pigment epithelium （RPE） cells and the probable mechanisms. Methods Cultured human RPE cells were treated with various concentrations （10^-9, 10^-8, 10^-7, 10^-6 and 10^-5 mol·L^-1） of ATRA at different time points （6, 12, 24, 48, 72 and 96 h）. Cell proliferation was evaluated by cell count and MTT colorimetrie assay, and cell cycle analysis was performed by flow cytometry. Results The cell viability rates of ATRA treated group were decreased obviously, compared with control groups （P〈0.01）. The inhibitory rates of RPE cell proliferation had positive correlation with ATRA dose and time of action （r1 =0. 9926, P〈0.05; r2 =0. 9647, P〈0.05）. In ATRA groups, compared with non-ATRA treated groups, the cell number in G1 phase was increased （P〈0.05）, while in G0/G1 phase was decreased （P〈0.05）. Conclusion ATRA could inhibit the proliferation of human RPE cells in a dose-dependent and time-dependent manner by arresting cell cycle.