Xie Keliang, Lian Naqi, Kan Yufei, Yang Man, Pan Jiacheng, Yu Yang, Yu Yonghao
Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Institute of Anesthesiology, Tianjin, China.
Department of Anesthesiology of Grade 2016, Tianjin Medical University, Tianjin, China.
Brain Res. 2020 Nov 1;1746:147003. doi: 10.1016/j.brainres.2020.147003. Epub 2020 Jun 27.
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 (H) 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% H 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 H 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% H 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 H. In addition, H could regulate the immune and the coagulation systems. Furthermore, western blot analysis revealed that H 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 H on SAE and contribute to the clinical application of H in patients with sepsis.
脓毒症脑病（SAE）在脓毒症患者中发病率和死亡率较高；然而，目前尚无有效的治疗方法。我们之前的研究报道，吸入2%氢气（H）对脓毒症和SAE具有保护作用；然而，具体机制尚未完全阐明。在本研究中，雄性癌症研究所小鼠被用于建立盲肠结扎和穿刺（CLP）模型或进行假手术，随后在假手术或CLP手术后1小时和6小时开始吸入2% H气体60分钟。采用基于相对和绝对定量等压标签（iTRAQ）的定量蛋白质组学结合液相色谱-串联质谱（LC-MS/MS）分析、苏木精和伊红（H&E）染色、尼氏染色和蛋白质印迹分析，研究H对脓毒症小鼠脑损伤的影响。H&E和尼氏染色结果表明，CLP小鼠存在明显的脑损伤，其特征为病理损伤加重，而吸入2% H可使其减轻。基于iTRAQ结合LC-MS/MS分析的定量蛋白质组学共鉴定出5317种蛋白质，其中39种与H的保护机制有关。此外，H可调节免疫和凝血系统。此外，蛋白质印迹分析显示，H通过下调SMAD4、DPYS、PTGDS的蛋白表达水平并上调CUL4A的表达水平，降低脓毒症小鼠的SAE。这些结果为H对SAE产生积极作用的机制提供了见解，并有助于H在脓毒症患者中的临床应用。
