【作者】 赵艳； 刘影； 朴莉花； 吴坤；

【Author】 ZHAO Yan~1,LIU Ying~1,PIAO Li-hua~2,WU Kun~1 (1.Department of Nutrition and Food Hygiene,Public Health College,Harbin Medical University, Harbin 150081,China;2.Harbin Acheng Center for Disease Control and Prevention,Harbin 150300, China)

【机构】 哈尔滨医科大学公共卫生学院营养与食品卫生学教研室； 哈尔滨市阿城区疾病预防控制中心；

【摘要】 背景与目的 :探讨贝特类降脂药作为过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptorα,PPARα)的配体对肌细胞的毒性及其作用机制。材料与方法:采用WST-1法测定苯扎贝特和吉非贝齐对人横纹肌肉瘤(RD)细胞的毒性作用;Hoechst 33342染色法观察细胞凋亡的形态学改变;Western blot法检测p-Akt与Akt的蛋白表达水平。结果 :苯扎贝特与吉非贝齐均明显抑制RD细胞的生长,呈剂量-效应关系。苯扎贝特引起细胞凋亡的典型变化,p-Akt/Akt蛋白表达的比值明显下降,MK886存在时比值未发生明显变化。结论 :苯扎贝特可能通过调节Akt表达,诱导细胞凋亡而引起肌细胞损伤。更多还原

【Abstract】 BACKGROUND:To investigate the myotoxicity of lipid-lowering fibrates as peroxisome proliferator-activated receptorα(PPARα) ligands to muscle cells.MATERIAL AND METHODS:WST-1 assay was used to assess the cytotoxicity of bezafibrate and gemfrozil to human embryo rhabdomyosarcoma(RD) cells.Hoechst 33342 staining was applied to determine apoptosis. The levels of p-Akt and Akt protein expression were detected by western blot.RESULTS:Both bezafibrate and gemfibrozil obviously caused a dose-dependent decrease in cell viability.Bezafibrate induced typical apoptosis,reduced ratio of p-Akt to Akt and the ratio was unchanged by bezafibrate in the presence of MK886,a PPARαantagonist.CONCLUSION:Fibrates as PPARαligands induced obvious cytotoxicity to RD cells.Bezafibrate might cause myopathy via downregulating Akt and inducing apoptosis.更多还原