高游离脂肪酸通过FOXO1途径抑制内皮祖细胞增殖并促进其凋亡

摘要

目的:研究高游离脂肪酸(FFA)对糖尿病患者内皮祖细胞(EPCs)增殖及凋亡的影响,评价FFA在糖尿病血管并发症中的可能作用.方法:分离培养2型糖尿病患者EPCs(DM组)和正常对照组EPCs(对照组),加入不同浓度(0、10和50 mmol/L)的FFA.MTT法检测EPCs增殖,Annexin-V/PI法检测其凋亡.RT-PCR法和Western blotting法检测核转录因子FOXO1的表达水平.结果:随着FFA浓度的增加,DM组和对照组EPCs增殖率明显下降,而凋亡率明显增加,差异均显著(P＜0.05).相同FFA浓度下,DM组增殖率低于对照组(P＜0.05).随着FFA浓度的增加,DM组和对照组FOXO1的mRNA表达逐渐降低,差异显著(P＜0.05).结论:高FFA可能通过FOXO1途径抑制EPCs增殖并诱导其凋亡,可能在糖尿病血管并发症的发生中发挥作用.%AIM: To investigate the effect of free fatty acid ( FFA ) on endothelial progenitor cells ( EPCs ), and to elucidate the role of FFA in the pathogenesis of diabetic peripheral vascular disease.METHODS: EPCs were isolated from the patients with type 2 diabetes mellitus ( DM group ) and normal healthy persons ( control group ).Various concentrations of FFA were added to the culturing system.MTT assay was used to detect the proliferative rate.Apoptotic rate of EPCs was measured by Annexin V/PI assay.The expression of FOXO1 was determined by RT - PCR and Western blotting.RESULTS: In a dose - dependent manner, FFA attenuated the proliferative activity of EPCs in both control group and DM group, while increased the apoptotic rates ( P ＜ 0.05 ).The expression of FOXO1 decreased under the condition of FFA exposure and the difference was significant ( P ＜0.05 ).CONCLUSION: FFA may be a new factor in the pathogenesis of diabetic peripheral vascular disease through FOXO1 pathway.