Objectives: Paraquat (PQ) poisoning can induce mitophagy and pulmonary fibrosis. Cyclosporine A (CsA) is an inhibitor of mitophagy. This study aimed at investigating whether CsA could inhibit PQ-induced mitophagy and pulmonary fibrosis in rats.Materials and Methods: Male Sprague-Dawley (SD) rats were treated with vehicle saline (control), 50 mg/kg PQ by gavage alone, or together with different doses of CsA. At 14 days post-induction, the levels of pulmonary fibrosis and PTEN-induced putative kinase 1 (PINK1) and Parkin expression in individual rats and mitochondrial membrane potential (MMP) in lung cells were measured. Moreover, A549 cells were treated with PQ or PQ + CsA for 24 h and the levels of PINK1, Parkin, fibronectin, collagen I and LC3 I and II expression and MMP were examined. Finally, the impact of PINK1 overexpression on the PQ or PQ + CsA-modulated fibronectin and collagen I expression in A549 cells was tested.Results: PQ exposure significantly increased the levels of hydroxyproline and collagen I expression and collagen fiber accumulation in the lung of rats, which were mitigated by CsA treatment. Furthermore, treatment with CsA significantly improved the PQ-decreased MMP and abrogated PQ-upregulated PINK1 and Parkin expression in the lungs of rats. In addition, CsA treatment decreased the PQ-induced fibrosis and mitophagy and PQ-impaired MMP as well as PQ-upregulated PINK1 and Parkin expression in A549 cells. The later effect of CsA was abrogated by PINK1 overexpression in A549 cells.Conclusions: Therefore, CsA can inhibit the PQ-induced mitophagy and pulmonary fibrosis by attenuating the PINK1/Parkin signaling.

中文翻译：

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环孢霉素可减轻百草枯引起的线粒体吞噬和肺纤维化。

目的：百草枯（PQ）中毒可引起线粒体吞噬和肺纤维化。环孢霉素A（CsA）是线粒体抑制剂。这项研究旨在调查CsA是否可以抑制大鼠PQ引起的线粒体和肺纤维化。材料与方法：雄性Sprague-Dawley（SD）大鼠分别用生理盐水（对照组），50 mg / kg PQ单独管饲法治疗，或以及不同剂量的CsA。诱导后第14天，测量每只大鼠的肺纤维化和PTEN诱导的假定激酶1（PINK1）和Parkin表达水平，以及肺细胞中的线粒体膜电位（MMP）。此外，将A549细胞用PQ或PQ + CsA处理24小时，并检测PINK1，帕金，纤连蛋白，胶原蛋白I和LC3 I和II以及MMP的水平。最后，测试了PINK1的过量表达对A549细胞中PQ或PQ + CsA调节的纤连蛋白和胶原蛋白I表达的影响。通过CsA治疗得以缓解。此外，用CsA处理可显着改善大鼠肺中PQ降低的MMP并消除PQ上调的PINK1和Parkin表达。此外，CsA处理降低了A549细胞中PQ诱导的纤维化和线粒体和PQ受损的MMP以及PQ上调的PINK1和Parkin表达。结论：因此，CsA可以通过减弱PINK1 / Parkin信号传导来抑制PQ诱导的吞噬和肺纤维化。