Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China.
Biomed Res Int. 2020 Jan 30;2020:1568209. doi: 10.1155/2020/1568209. eCollection 2020.
Enhancement of mitochondrial physiological function prevents sepsis-induced dysfunction. The present study aimed to elucidate the mechanism by which hydrogen (H) affects mitochondrial function in a wild-type (WT) and homozygous nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (KO, Nrf2) murine model of sepsis. In myocardial tissues with severe sepsis, H gas treatment reduced mitochondrial dysfunction, whereas zinc protoporphyrin (ZnPPIX) negated these beneficial effects. H treatment upregulated the protein expression of mitofusin-2 (Mfn2), peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1), and protein heme oxygenase-1 (HO-1) in WT mice with severe sepsis but not in their Nrf2 counterparts, and this upregulation was inhibited in the presence of ZnPPIX. In conclusion, the mechanism by which H limits organ damage in mice with severe sepsis involves HO-1, whereas the mechanism that limits severe sepsis-related mitochondrial dysfunction involves both HO-1 and Nrf2.
增强线粒体生理功能可预防脓毒症引起的功能障碍。本研究旨在阐明氢气（H）如何影响野生型（WT）和纯合核因子红细胞 2 相关因子 2（Nrf2）敲除（KO，Nrf2）脓毒症小鼠模型中线粒体功能。在严重脓毒症的心肌组织中，H 气体处理可减轻线粒体功能障碍，而锌原卟啉（ZnPPIX）则否定了这些有益作用。H 处理可上调 WT 严重脓毒症小鼠的线粒体融合蛋白 2（Mfn2）、过氧化物酶体增殖物激活受体-γ共激活因子 1（PGC-1）和血红素加氧酶-1（HO-1）的蛋白表达，但在 Nrf2 对应物中则没有，并且在存在 ZnPPIX 的情况下，这种上调被抑制。总之，H 限制严重脓毒症小鼠器官损伤的机制涉及 HO-1，而限制严重脓毒症相关线粒体功能障碍的机制则同时涉及 HO-1 和 Nrf2。
