线粒体通透转换孔开放与NAFLD大鼠肝细胞凋亡的关系

Opening of the mitochondrial permeability transition pore in development of non-alcoholic fatty liver disease in rats

目的探讨大鼠非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)发生发展过程中线粒体通透转换孔(mitochondrial permeability transition pore,MPTP)状态改变,及其与肝细胞凋亡的关系。方法24只雄性SD大鼠随机分为对照组与实验组,对照组6只给予正常鼠食,8周后处死;实验组18只给予高脂饮食。分别于饲养4、8、12周时处死。提取线粒体,分光光度计检测线粒体通透转换孔的状态变化,流式细胞术检测肝细胞凋亡情况。结果线粒体通透转换孔开放率随高脂饮食饲养时间延长明显增加,肝细胞凋亡比例亦明显增加。结论大鼠非酒精性脂肪性肝病肝细胞凋亡与线粒体通透转换孔有关。线粒体通透转换孔可能参与非酒精性脂肪肝向非酒精性脂肪性肝炎转变的“二次打击”过程。

Objective To investigate the change of the mitoehondrial permeability transition pore＇s state in the development of non-alcoholic fatty liver disease in rats, and its relation with the liver apoptosis. Methods The liver mitochondrion was isolated from the fatty liver rats. The opening of the mitochondrial permeability transition pore was detected with Ca^2＋ induction, which method was based on the absorbance changes of the mitochondrial suspension at 540nm. The liver apoptosis was detected with the flow cytometer. Results As the liver lesion increased, the ratio of the opening of the mitochondrion permeability transition pore to the total mitochondrion increased, and the ratio of apoptosis grew higher. Conclusion The remarkable changes of mitochondrial permeability transition during rat fatty liver disease may be the basis of the apoptosis of the non-alcoholic fatty liver, and it may also be related to the initiation and the end of non-alcoholic steatohepatisis.