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环孢素A对百草枯中毒大鼠线粒体自噬导致的肺纤维化作用研究
刘开翔
0
(川北医学院第二临床医学院·南充市中心医院肾内科)
摘要:
【摘要】 目的 建立百草枯(PQ)中毒大鼠模型,探讨环孢素A(CsA)对PQ中毒大鼠肺线粒体自噬的作用及机制。方法 成年雄性SD大鼠54只,随机分为正常对照组(n=12)、PQ组(n=24),CsA大、中、小剂量组(n=18)。PQ组下设1天、3天、7天和14天4个时间点,每个时间点每个剂量组各6只大鼠。使用20%PQ溶液50 mg/kg一次性灌胃建立大鼠PQ中毒模型,并以自噬发生明显的时间点作为CsA干预时间点。各CsA干预组在给予20%PQ溶液灌胃的前3天开始分别予环孢素5 mg/(kg·d)、10 mg/(kg·d)、15 mg/(kg·d)灌胃。通过Masson染色观察PQ中毒后肺组织病理损害,JC1染色检测肺组织线粒体膜电位变化,Western blot检测调控线粒体自噬关键性蛋白PINK1、Parkin的水平变化。结果 与正常对照组相比,随着PQ中毒时间的延长,PQ中毒大鼠肺纤维化病理评分升高,肺组织JC1红绿荧光比降低,PINK1及Parkin蛋白表达均升高,差异有统计学意义(P<001)。与PQ组比较,环孢素A组大鼠肺组织肺纤维化病理评分、PINK1及Parkin蛋白均下降,差异有统计学意义(P<0.05),JC1红绿荧光比升高,差异有统计学意义(P<005)。结论 环孢素A可通过影响PINK1/Parkin蛋白,减轻百草枯中毒引起的线粒体自噬,改善肺纤维化。
关键词:  百草枯  肺纤维化  线粒体自噬  PINK1  Parkin
DOI:
基金项目:四川省教育厅课题(16ZA0240);南充市科技局(2015 855)
Effect of cyclosporin a on pulmonary fibrosis induced by mitochondria autophagy in rats with paraquat poisoning
LIU Kaixiang
(Department of Nephrology, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College)
Abstract:
【Abstract】 Objective To investigate the effect and mechanism of cyclosporine A on the occurrence of pulmonary fibrosis in paraquat poisoning. Methods 60 adult male SpragueDawley (SD) rats were randomly divided into normal group (n=12), PQ group (n=30), CsA high, medium and low dose group (n=18). PQ group rats were divided into four time points: 1 day, 3 days, 7 days and 14 days. Each time point included 6 rats. 20% PQ solution (50 mg/kg) were selected for once administration gavage . Choose the time point of autophagy occurred evidently as CsA intervention time point. Each CsA group was administration gavage CsA with dose 5 mg/(kg·day), 10 mg/(kg·day) and 15mg/(kg·day) before gavage PQ. The change of lung tissue pathological lesion, lung tissue′s mitochondrial transmembrane potential (MMP), PINK1 and Parkin were measured.Results Compared with that of normal group, the degrees of pulmonary fibrosis, the PINK1 and Parkin of PQ groups were gradually increased and the red/ green fluorescence ratio of PQ groups was decreased (P<001). The degrees of pulmonary fibrosis, the PINK1 and Parkin of CsA groups were lower than that of PQ groups (P<005). The red/ green fluorescence ratio of CsA groups was higher than that of PQ groups (P<005). ConclusionCyclosporine A can reduce PINK1 / Parkin protein, mitigate the mitochondrial autophagy caused by paraquat poisoning and improve pulmonary fibrosis.
Key words:  Paraquat  Pulmonary fibrosis  Mitophagy  PINK1  Parkin

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