Dexmedetomidine ameliorates endotoxin-induced acute lung injury in vivo and in vitro by preserving mitochondrial dynamic equilibrium through the HIF-1a/HO-1 signaling pathway

• DOI: 10.1016/j.redox.2021.101954
• Publication Date: 2021-03-21T15:02:35Z
• Authors: Jia Shi; Tianxi Yu; Kai Song; Shihan Du; Simeng He; Xinxin Hu; Xiangyun Li; Haibo Li; Shuan Dong; Yuan Zhang; Zilei Xie; Cui Li; Jianbo Yu
• Keywords: Lipopolysaccharides; Medicine (General); QH301-705.5; Acute Lung Injury; Mitochondrial Dynamics; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; R5-920; Endotoxin; Acute lung injury; Hypoxia-inducible factor 1; Animals; Biology (General); 0303 health sciences; Rats; 3. Good health; Endotoxins; Mice, Inbred C57BL; Oxidative Stress; Heme oxygenase-1; Mitochondrial dynamics; Dexmedetomidine; Research Paper; Signal Transduction

Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded protection by regulating process mitochondrial dynamics through HIF-1a/HO-1 pathway in vivo vitro. Using C57BL/6J mice exposed to lipopolysaccharide, it was initially observed preemptive administration (50μg/kg) alleviated pathologic injury, reduced oxidative stress indices (OSI), improved dysfunction, upregulated expression HIF-1α HO-1, accompanied shifting dynamic course mitochondria into fusion. Moreover, HO-1-knockout or HO-1 siRNA transfected NR8383 cells were pretreated with stabilizer DMOG validate effect on DEX-mediated a model endotoxin-induced injury. We found pretreatment distinctly relieved decreased levels ROS mtDNA, OSI, increased nuclear accumulation HIF-1a protein wild type but not KO mice. Similar observations recapitulated NC after LPS stimulation cells. Concertedly, reversed impaired morphology stimulated-wild cells, fusion protein, while downregulated fission dependent pathway. Altogether, our data both vitro certified treatment ameliorated preserving equilibrium fusion/fission regulation signaling