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目的:研究曲格列酮的肝细胞毒性及其可能的机制。方法:在原代大鼠肝细胞模型和其他3种不同来源非肝细胞系,用WST-1法、乳酸脱氢酶释放法、荧光检测法、生物发光法等方法,观察曲格列酮对肝细胞的损伤作用。结果:不同剂量曲格列酮作用后,其在原代培养大鼠肝细胞的IC_(50)值最低,即其对原代肝细胞毒性最大。曲格列酮诱导活性氧(ROS)生成,并引起还原型谷胱甘肽(GSH)和ATP水平比对照细胞显著降低。不同剂量的曲格列酮作用5h后诱发肝细胞凋亡、坏死。结论:曲格列酮对大鼠肝细胞的毒性作用强于对其他非肝细胞来源细胞的毒性作用。曲格列酮可以引起肝细胞氧化性损伤,肝细胞凋亡和坏死。
Objective: To study the hepatotoxicity of troglitazone and its possible mechanism. Methods: In the primary rat hepatocyte model and three other non-hepatoma cell lines with different sources, the effects of troglitazone on the liver were observed by the methods of WST-1, lactate dehydrogenase release, fluorescence detection and bioluminescence Cell injury. Results: After treated with different doses of troglitazone, IC 50 value of primary cultured rat hepatocytes was the lowest, that is, it had the highest toxicity to primary hepatocytes. Troglitazone induced reactive oxygen species (ROS) production and caused a significant decrease in reduced glutathione (GSH) and ATP levels compared with control cells. Different doses of troglitazone induced hepatocyte apoptosis and necrosis after 5h. Conclusion: Toxicological effects of troglitazone on rat hepatocytes are stronger than those on other non-hepatocyte-derived cells. Troglitazone can cause hepatocellular oxidative damage, hepatocyte apoptosis and necrosis.