Sepsis encephalopathy (SAE) has a high incidence and mortality rate in patients with sepsis; however, there is currently no effective treatment. Our previous studies have reported that 2% hydrogen (H2) gas inhalation had a protective effect on sepsis and SAE; however, the specific mechanism have not been fully elucidated. In the current study, male Institute of Cancer Research mice were either used to create the cecal ligation and puncture (CLP) model or for sham surgery, followed by 2% H2 gas inhalation for 60 min beginning at 1 and 6 h following sham or CLP surgeries. The isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, hematoxylin and eosin (H&E) staining, Nissl staining, and western blot analysis were used to investigate the effects of H2 on brain injury in mice with sepsis. The results of the H&E, and Nissl staining indicated that the CLP mice had a significant brain injury, which was characterized by aggravated pathological damage and was alleviated by 2% H2 inhalation. Quantitative proteomics based on iTRAQ combined with LC-MS/MS analysis quantified a total of 5317 proteins, of which 39 were connected with the protective mechanism of H2. In addition, H2 could regulate the immune and the coagulation systems. Furthermore, western blot analysis revealed that H2 decreased SAE in septic mice by downregulating the protein expression levels of SMAD4, DPYS, PTGDS and upregulating the expression level of CUL4A. These results provide insights into the mechanism of the positive effect of H2 on SAE and contribute to the clinical application of H2 in patients with sepsis.
Keywords: Hydrogen gas; Isobaric tags for relative and absolute quantitation; Proteomics; Sepsis; Sepsis-related encephalopathy.
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