Zhao Runmin, Wang Bingxia, Wang Dasheng, Wu Benhe, Ji Peiyu, Tan Dingyu
Department of Emergency Medicine, Northern Jiangsu People's Hospital, Yangzhou University College of Clinical Medicine, Yangzhou 225001, China.
Oxid Med Cell Longev. 2021 Feb 26;2021:6675264. doi: 10.1155/2021/6675264. eCollection 2021.
Acute lung injury (ALI) is a serious respiratory syndrome characterized with uncontrolled inflammatory response. Oxyberberine has strong potential for clinical usage since it showed strong anti-inflammatory, antifungal, and antiarrhythmic effects in various diseases. In the present study, we evaluated whether oxyberberine can inhibit lipopolysaccharide- (LPS-) induced ALI and further evaluated the possible involvement of mitophagy by using A549 cells, a human lung epithelial cell line. Our study shows that oxyberberine significantly inhibited LPS-induced lung pathological injury and lung edema, as indicated by the changes in lung wet/dry ratio and total protein levels in the BALF in mice. Moreover, oxyberberine inhibited inflammation, as indicated by the changes of neutrophil accumulation and production of proinflammatory cytokines including tumor necrosis factor (TNF-), interleukin 1 (IL-1), and IL-6 in both the lung and bronchoalveolar lavage fluid (BALF) in ALI mice. Our in vitro study shows that LPS significantly decreased the protein level of mitochondrial proteins, including cytochrome c oxidase subunit IV (COX IV), p62, and mitofusin-2 (Mfn2) in A549 cells. In addition, LPS induced significant Parkin1 translocation from cytoplasm to mitochondria. These changes were significantly inhibited by oxyberberine. Notably, the inhibitory effect of oxyberberine was almost totally lost in the presence of lysosome fusion inhibitor bafilomycin A1 (Baf), a mitophagy inhibitor. In conclusion, the present study demonstrated that oxyberberine alleviated LPS-induced inflammation in ALI via inhibition of Parkin-mediated mitophagy.
急性肺损伤（ALI）是一种以失控性炎症反应为特征的严重呼吸综合征。氧化小檗碱具有很强的临床应用潜力，因为它在多种疾病中表现出强大的抗炎、抗真菌和抗心律失常作用。在本研究中，我们评估了氧化小檗碱是否能抑制脂多糖（LPS）诱导的ALI，并通过使用人肺上皮细胞系A549细胞进一步评估了线粒体自噬可能的参与情况。我们的研究表明，氧化小檗碱显著抑制了LPS诱导的肺病理损伤和肺水肿，这通过小鼠肺湿/干比和支气管肺泡灌洗液（BALF）中总蛋白水平的变化得以体现。此外，氧化小檗碱抑制了炎症，这通过ALI小鼠肺和支气管肺泡灌洗液（BALF）中中性粒细胞积聚以及促炎细胞因子包括肿瘤坏死因子（TNF-）、白细胞介素1（IL-1）和IL-6的产生变化得以体现。我们的体外研究表明，LPS显著降低了A549细胞中线粒体蛋白的水平，包括细胞色素c氧化酶亚基IV（COX IV）、p62和线粒体融合蛋白2（Mfn2）。此外，LPS诱导Parkin1从细胞质显著转位至线粒体。这些变化被氧化小檗碱显著抑制。值得注意的是，在溶酶体融合抑制剂巴弗洛霉素A1（Baf）（一种线粒体自噬抑制剂）存在的情况下，氧化小檗碱的抑制作用几乎完全丧失。总之，本研究表明氧化小檗碱通过抑制Parkin介导的线粒体自噬减轻了LPS诱导的ALI炎症。
