The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, China.
Department of Pathology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, China.
Biomed Res Int. 2020 Jul 30;2020:9329427. doi: 10.1155/2020/9329427. eCollection 2020.
MitoTEMPO, a mitochondrial antioxidant, has protective effects on liver-related diseases. However, the role of MitoTEMPO on nonalcoholic fatty liver disease (NAFLD) and its possible mechanisms are largely unknown. Here, we investigated the effects of MitoTEMPO on NAFLD using high fat diet- (HFD-) induced obese mice as animal models. MitoTEMPO was intraperitoneally injected into HFD mice. Liver morphological changes were observed by H&E and Oil Red O staining, and the frequency of MDSCs in peripheral blood was analyzed by flow cytometry. Moreover, real-time quantitative PCR, western blot, and immunohistochemistry were conducted to detect the mRNA and protein expressions in the liver tissues. The results showed that the hepatic steatosis in liver tissues of HFD mice injected with MitoTEMPO was significantly ameliorated. Additionally, MitoTEMPO reduced the frequency of CD11bGr-1 MDSCs in peripheral circulation and decreased Gr-1 cell accumulation in the livers. Further studies demonstrated that MitoTEMPO administration suppressed the mRNA and protein expressions of MDSC-associated proinflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein A8 (S100A8), and S100 calcium-binding protein A9 (S100A9). Our results suggest that MitoTEMPO appears to be a potential chemical compound affecting certain immune cells and further ameliorates inflammation in obese-associated NAFLD.
MitoTEMPO 是一种线粒体抗氧化剂，对肝脏相关疾病具有保护作用。然而，MitoTEMPO 对非酒精性脂肪性肝病（NAFLD）的作用及其可能的机制在很大程度上尚不清楚。在这里，我们使用高脂肪饮食（HFD）诱导的肥胖小鼠作为动物模型，研究了 MitoTEMPO 对 NAFLD 的影响。MitoTEMPO 通过腹腔注射到 HFD 小鼠中。通过 H&E 和油红 O 染色观察肝组织形态变化，通过流式细胞术分析外周血中 MDSC 的频率。此外，进行实时定量 PCR、western blot 和免疫组织化学检测肝组织中 mRNA 和蛋白的表达。结果表明，MitoTEMPO 注射的 HFD 小鼠肝组织中的肝脂肪变性明显改善。此外，MitoTEMPO 降低了外周循环中 CD11bGr-1 MDSC 的频率，并减少了 Gr-1 细胞在肝脏中的积累。进一步的研究表明，MitoTEMPO 给药抑制了 MDSC 相关促炎介质的 mRNA 和蛋白表达，如单核细胞趋化蛋白-1（MCP-1）、S100 钙结合蛋白 A8（S100A8）和 S100 钙结合蛋白 A9（S100A9）。我们的研究结果表明，MitoTEMPO 似乎是一种潜在的影响某些免疫细胞的化学化合物，并进一步改善肥胖相关 NAFLD 中的炎症。
