川北医学院学报2017，Vol.32Issue(3)：324-328,5.DOI:10.3969/j.issn.1005-3697.2017.03.003
线粒体自噬在百草枯中毒大鼠模型肺纤维化中的作用研究
To evaluate the effects of mitophagy in paraquat-induced rat pulmonary fibrosis model
摘要
Abstract
Objective:To investigate the effect of mitophagy on the occurrence of pulmonary fibrosis in paraquat poisoning by observe the changes of JC-1, PINK1,Parkin and the reactive oxygen species(ROS)in different stages of paraquat-induced rat pulmonary fibrosis model.Methods:42 adult male sprague-dawley (SD) rats were randomly divided into normal group(n=6) and PQ group(n=36).PQ group rats were divided into six time points:2 h,12 h,24 h,72 h,7 d,14 d,each time point includes 6 rats.20% PQ solution with adose of 50 mg/kg were selected for once administration gavage to establish PQ poisoning model,through the detection of red blood cell ROS concentration by flow cytometry,HE staining and Masson staining of lung tissue damage was observed after PQ poisoning,JC-1 staining was used to detect the changes of mitochondrial membrane potential changes in lung tissue,PINK1,Parkin protein was detected by Western blot.Results:Compared with normal group,the degrees of pulmonary fibrosis was gradually increased with the increase of PQ poisoning time,the difference was significant (P<0.05).In the PQ groups, the positive rate of ROS fluorescence intensity increased significantly at 2h after poisoning,and peaked at 12 h after poisoning, and then decrease gradually(P<0.05),the difference between normal group and 14 d after poisoning has no statistical significance (P>0.05).The ratio of JC-1,red green fluorescence in lung tissue of PQ group was lower than that of control group,and Western and blot indicated that the expression of PINK1 and Parkin protein increased with the duration of poisoning, and the difference was statistically significant (P<0.01).Pearson test shows there is a negative correlation between the red green fluorescence ratio and PINK1,Parkin and the pathology score of pulmonary fibrosis.(r=-0.890,P<0.01;r=-0.845,P<0.01;r=-0.794,P<0.01).In 12 h after PQ poisoning,there is a negative correlation between the ratio of the positive rate of ROS fluorescence intensity in erythrocyte and the red green fluorescence (r=-0.712,P<0.01),and a positive correlation between the positive rate of ROS fluorescence intensity and PINK1,Parkin and the pathology score of pulmonary fibrosis(r=0.571,P<0.01;r=0.484,P<0.01;r=0.602,P<0.05).Conclusion:The mitophagy and oxidative stress were induced by PQ poisoning.The generation of ROS closely related to the development of autophagy in mitochondria and is involved in the development of pulmonary fibrosis in PQ rats.关键词
百草枯/肺纤维化/线粒体自噬/PINK1/Parkin/氧化应激Key words
Paraquat/Pulmonary fibrosis/Mitophagy/PINK1/Parkin/Oxidative stress分类
医药卫生引用本文复制引用
刘开翔,占志朋,谢席胜..线粒体自噬在百草枯中毒大鼠模型肺纤维化中的作用研究[J].川北医学院学报,2017,32(3):324-328,5.基金项目
四川省科技厅基金项目(2011JTD0014) （2011JTD0014）
南充市科技局基金项目(2015-855) （2015-855）
