Hu Kai, Xiao Lidan, Li Longjiang, Shen Yi, Yang Yongqiang, Huang Jiayi, Wang Yaping, Zhang Li, Wen Sha, Tang Li
Laboratory of Stem cell and Tissue Engineering, Chongqing Medical University, Chongqing, China; Department of Histology and Embryology, Chongqing Medical University, Chongqing, China.
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Immunol Lett. 2021 Dec;240:24-30. doi: 10.1016/j.imlet.2021.09.003. Epub 2021 Sep 12.
The mitochondria are the primary source of reactive oxygen species (ROS) under pathological condition, but the significance of mitochondrial ROS in the development of Lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute liver injury remains unclear. In the present study, the level of mitochondrial ROS in LPS/D-Gal has been determined by MitoSox staining and the potential roles of mitochondrial ROS in LPS/D-Gal-induced liver injury have been investigated by using the mitochondria-targeting antioxidant MitoQ. The results indicated that LPS/D-Gal exposure induced the generation of mitochondrial ROS while treatment with MitoQ reduced the level of mitochondrial ROS. Treatment with MitoQ ameliorated LPS/D-Gal-induced histopathologic abnormalities, suppressed the elevation of AST and ALT, and increased the survival rate of the experimental animals. Treatment with MitoQ also suppressed LPS/D-Gal-induced production of tumor necrosis factor α (TNF-α), inhibited the activities of caspase-3, caspase-8 and caspase-9, decreased the level of cleaved caspase-3 and reduced the counts of TUNEL positive cells. These results indicate that mitochondrial ROS is involved in the development of LPS-induced acute liver injury and the mitochondria-targeting antioxidant MitoQ might have potential value for the treatment of inflammation-based acute liver injury.
线粒体是病理状态下活性氧（ROS）的主要来源，但线粒体ROS在脂多糖（LPS）/D-半乳糖胺（D-Gal）诱导的急性肝损伤发生发展中的意义仍不清楚。在本研究中，通过MitoSox染色测定了LPS/D-Gal中活性氧的水平，并使用线粒体靶向抗氧化剂MitoQ研究了线粒体ROS在LPS/D-Gal诱导的肝损伤中的潜在作用。结果表明，LPS/D-Gal暴露诱导了线粒体ROS的产生，而用MitoQ处理降低了线粒体ROS的水平。用MitoQ处理改善了LPS/D-Gal诱导的组织病理学异常，抑制了AST和ALT的升高，并提高了实验动物的存活率。用MitoQ处理还抑制了LPS/D-Gal诱导的肿瘤坏死因子α（TNF-α）的产生，抑制了caspase-3、caspase-8和caspase-9的活性，降低了裂解的caspase-3的水平，并减少了TUNEL阳性细胞的数量。这些结果表明，线粒体ROS参与了LPS诱导的急性肝损伤的发生发展，线粒体靶向抗氧化剂MitoQ可能对基于炎症的急性肝损伤的治疗具有潜在价值。
