Aili Dong1, Yang Yu2, Yanyan Wang2, Can Li3, Hongguang Chen2, Yingxue Bian2, Peng Zhang4, Yungang Zhao3, Yonghao Yu5, Keliang Xie6. 1. Department of Anesthesiology, Tianjin First Center Hospital, Tianjin 300192, China. 2. Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. 3. Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of Sport, Tianjin 300381, China. 4. Department of Anesthesiology, Tianjin HaiBin People Hospital, Tianjin 300000, China. 5. Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: yuyonghao@126.com. 6. Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: xiekeliang2009@hotmail.com.
Abstract
BACKGROUND: Lungs are one of the most common target organs of sepsis [1]. Hydrogen gas (H2), 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% H2 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 + H2, CLP and CLP + H2. 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/FiO2), 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% H2 increased PaO2/FiO2 ratios, MMP and ATP levels, RCR, complex I activity and MFN2 expression but decreased histological score and Drp1 levels in the presence of sepsis. These data indicated that inhalation of 2% H2 to regulate mitochondrial function and dynamics may be a promising therapeutic strategy for lung injuries induced by severe sepsis.
BACKGROUND: Lungs are one of the most common target organs of sepsis [1]. Hydrogen gas (H2), 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% H2 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 + H2, CLP and CLP + H2. 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/FiO2), 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% H2 increased PaO2/FiO2 ratios, MMP and ATP levels, RCR, complex I activity and MFN2 expression but decreased histological score and Drp1 levels in the presence of sepsis. These data indicated that inhalation of 2% H2 to regulate mitochondrial function and dynamics may be a promising therapeutic strategy for lung injuries induced by severe sepsis.