摘要
目的探讨阿托伐他汀对低氧环境下人脐静脉内皮细胞(HUVECs)增殖和细胞周期的影响。方法将培养的HUVECs随机平均分为5组,每组8孔。正常对照组给予血清DMEM液培养12 h;低氧模型组置于低氧装置中用无血清DMEM液培养12 h;低、中、高浓度给药组均置于低氧装置中,分别用含0.05,0.10,0.20 mmol.L-1阿托伐他汀钙的无血清DMEM液培养12 h。采用MTT法测定细胞增殖情况,流式细胞术分析各组不同周期细胞所占比例。结果低氧模型组细胞增殖被明显抑制。在低氧环境下分别加入阿托伐他汀后,细胞增殖过程被明显促进,与低氧模型组相比,各浓度给药组差异有显著性或极显著性(P<0.05或P<0.01),但药物浓度与效应呈非线性关系,其中中浓度组促增殖作用最强,而高浓度组促增殖作用明显减弱。给予不同浓度阿托伐他汀干预后,HUVECs细胞周期中S期细胞显著增多,G0/G1期细胞所占比例下降。结论适当浓度的阿托伐他汀对低氧环境下HUVECs的增殖和DNA的合成有促进作用,阿托伐他汀在缺血心肌新生血管形成过程中可能具有一定作用。
Objective To probe into the effects of atorvastatin on the proliferation and cell cycle of cultured human umbilical vein endothelial cells （ HUVECs ） in a hypoxic environment. Methods HUVECs were cultured in a DMEM medium with 10% fetal calf serum in 24 well plates with a concentration of 1 × 10^5 cells per well. The cells were then randomly divided into 5 groups, with 8 wells of cells per group. Cells of the normal control group were further incubated in a serum-free DMEM medium for 12 h under normoxic condition. Cells of the hypexia model group were further incubated in a serum-free DMEM medium for 12 h in a hypoxia device（ PO2 〈 1.0 kPa）. Cells of the low, medium and high dose trial groups were further incubated in a serum-free DMEM mediumn containing 0.05,0.10 and 0.20 mmol · L^-1 of atorvastatin, respectively, for 12 h in the hypoxia device. The proliferation of the cells was assayed with the MTT method while the preparations of cells in their different cycles were analyzed with flow cytomelry. Results Proliferation of the cells was strikingly depressed in the hypexic environment. Atorvastatin in different concentrations was shown to significantly promote the proliferation of the endothelial cells subjected to hypoxia （P 〈 0.05 or P 〈 0.01 as compared with cells of the hypoxia model group）. The dose-effect relationship, however, was not linear. Atorvastatin at the medium dose was shown to have the strongest effect in promoting the cell proliferationa. The drug at the high dose had a much weaker effects on the promotion of cell proliferation. Atorvastatin in different doses was also shown to result in significant increase in the proportion of the cells in S phase and reduce that of the cells in G0/G1 phase. Conclusion Atorvastatin in appropriate concentrations was shown to promote the proliferation and DNA synthesis of HUVECs in a hypoxic environment. It seems possible that atorvastatin may play a certain role in the neogenesis of blood vessels in the ischemic myocardium.
出处
《医药导报》
CAS
2006年第8期746-748,共3页
Herald of Medicine
关键词
阿托伐他汀
内皮细胞
低氧
细胞增殖
细胞周期
Atorvastatin
Endothelial cells
Hypexia
Cell proliferation
Cell cycle
