关键词: 氯贝丁酯;线粒体膜电位;细胞凋亡;自由基

Abstract:

Objective To explore the effect of clofibrate on freshly isolated mouse liver mitochondria and a cultured hepatocyte cell line, AML-12. Methods  Mitochondrial membrane potential was determined by using the fluorescent dye, JC-1. Levels of reactive oxygen species were measured with the fluorescent probes DCFDA. CsA and antioxidants such as Vitamin C, deferoxamine and catalase were used to protect cells. Results Application of clofibrate at concentrations greater than 0.3mmol/L rapidly collapsed the ΔΨm both in liver cells and in isolated mitochondria. The loss of ΔΨm occurred prior to cell death, as revealed by the protective effect of cyclosporin A (CsA) on the decrease in ΔΨm. Treatment  of hepatocytes with clofibrate caused a significant increase in intracellular and mitochondrial ROS. Antioxidants such as Vitamin C, deferoxamine, and catalase were able to protect cells against lofibrate-induced loss of viability. Conclusion  Clofibrate may impair mitochondrial function, stimulates formation of ROS, and eventually contributes to cell death.

Key words: Clofibrate； Mitochondrial membrane potential； Apoptosis； Free radicals