期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 65, 期 -, 页码 366-372出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2018.10.012
关键词
Sepsis; Acute lung injury; Molecular hydrogen; Mitochondrial dynamics; Mitochondrial dysfunction
资金
- National Natural Science Foundation of China [81671888, 81772043, 81471842]
Background: Lungs are one of the most common target organs of sepsis [1]. Hydrogen gas (H-2), which has selective anti-oxidative effects, can be effectively used to treat septic mice. Mitochondrial dysfunction and dynamics play important roles in sepsis-induced organ damage. Methods: By using cecal ligation and puncture (CLP), a classic septic model, we explored the role of 2% H-2, treatment in sepsis-induced acute lung injury (ALI) linked to mitochondrial function and dynamics. We randomized male Institute for Cancer Research (ICR) mice into 4 groups: sham, sham + H-2, CLP and CLP + H-2. At 24 h after CLP or sham operations, we used histological examination and transmission electron microscopy (TEM) to observe lung slices. We analyzed oxygenation index (PaO2/FiO(2)), mitochondrial-membrane potential (MMP), adenosine triphosphate (ATP) levels, respiration control ratio (RCR) and mitochondrial-respiration complex activities (I and II) using commercial kits, and dynamin-related protein 1 (Drp1) and mitofusin-2 (MFN2) using Western blot. Results: Therapy with 2% H-2 increased PaO2/FiO(2) ratios, MMP and ATP levels, RCR, complex I activity and MFN2 expression but decreased histological score and Drpl levels in the presence of sepsis. These data indicated that inhalation of 2% H-2 to regulate mitochondrial function and dynamics may be a promising therapeutic strategy for lung injuries induced by severe sepsis.
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