吡格列酮对游离脂肪酸介导βTc3细胞凋亡干预作用.docVIP

吡格列酮对游离脂肪酸介导βTc3细胞凋亡干预作用 　【摘要】 目的 研究吡格列酮对游离脂肪酸(FFA)诱导的小鼠胰岛βTc3细胞凋亡的影响及其作用机制。 方法 以βTc3细胞为研究对象,分为对照组及FFA组(0.25,0.5,1.0 mmol/L)。检测不同浓度FFA干预后βTc3细胞的增殖抑制率、细胞周期、细胞凋亡率;检测吡格列酮对FFA诱导的βTc3细胞凋亡的干预作用。 结果 FFA干预后的βTc3细胞增殖抑制率随FFA作用时间延长、浓度增加而进行性增加。各浓度FFA干预24 h后βTc3细胞周期于G1/S检测点明显阻滞,凋亡细胞比例增加。吡格列酮干预FFA诱导的βTc3细胞后24 h,βTc3细胞周期阻滞减少,凋亡细胞比例明显减少。 结论 FFA水平异常不利于胰岛βTc3细胞生存,并可诱导βTc3细胞凋亡;吡格列酮有助于维护在FFA诱导下的胰岛βTc3细胞的生存能力,并避免或减少其凋亡。 【关键词】 噻唑烷二酮类 脂肪酸类 菲酯化 胰岛 糖尿病 2型 细胞凋亡 ABSTRACT: Objective To investigate the effects of pioglitazone on FFAinduced apoptosis of βTc3 cell, a pancreatic βcell line in vitro. Methods βTc3 was subject to different treatments with a blank and three kind concentrations of FFA, that were 0.25, 0.5 and 1.0 mmol/L FFA. The Method of MTT was used to measure the proliferation inhibition rates for successive three days after FFA intervention. The changes of cell cycle were detected 24 hours after treatment by a flow cytometry. TUNEL was used to determine the apoptosis rate of cells 24 hours after treatment. TUNEL and flow cytometry were used to determine intervention effect of Pioglitazone on the apoptosis of βTc3 cell induced by FFA. Results Inhibition of βTc3 was increased with prolonged treatment of FFA and increased FFA concentrations. Flow cytometry analysis showed that cell cycle of βTc3 cell treated with FFA of all the concentration was blocked in phase of G1/S. The percentage of βTc3 cell apoptosis substantially increased due to FFA treatment. No obvious abnormal change of cell cycle of βTc3 cell and a substantially decrease of percentage of apoptosis cells after pioglitazone intervention. Conclusion Abnormal FFA level is extremely harmful for survival of βTc3 cell cultured in vitro, but pioglitazone could maintain the surviving ability of insulin βTc3 cell damaged by FFA. KEY WORDS: thiazolidinediones; PPAR gamma; fatty acids,nonesterified; diabetes mellitus,type 2; apoptosis 福建医科大学学报 2008年7月 第42卷第4期程惠希等：吡格列酮对游离脂肪酸介导的βTc3细胞凋亡的干预作用2型糖尿病是糖尿病的主要类型,但其发病机制尚未阐明。迄今的研究显示,胰岛β细