未经证实:神经炎症在脓毒症相关性脑病(SAE)的病理生理中起重要作用。肠道菌群和肠道脑轴被认为是神经系统疾病发展的重要介质。本研究旨在探讨肠道菌群在脓毒症相关脑损伤中的作用及其机制。
UNASSIGNED:使用盲肠结扎和穿孔(CLP)建立SAE的小鼠模型。根据小鼠死亡率和相关的死亡时间,对轻度SAE(LSAE)和重度SAE(SSAE)进行分类。进行粪便微生物群移植(FMT)以验证肠道微生物群的作用。术前收集的两组小鼠粪便进行16S和靶向短链脂肪酸测序。
未经证实:来自SSAE和LSAE小鼠的肠道微生物群显示出不同的功能。有趣的是,与SSAE小鼠相比,LSAE小鼠产生更多的丁酸。在体内实验中,丁酸钠(NaB)降低了小鼠海马中的高氧化应激水平,并赋予脓毒症小鼠明显的生存优势。此外,NaB阻止了LPS刺激的原代小胶质细胞中细胞内活性氧(ROS)生成和诱导型一氧化氮合酶表达的增加。发现GPR109A/Nrf2/HO-1信号通路参与丁酸钠诱导的原代小胶质细胞抗氧化反应的激活。
未经批准:我们的研究结果表明肠道微生物群在SAE易感性中的关键作用。丁酸,肠道微生物群的代谢产物,GPR109A/Nrf2/HO-1通路在脓毒症过程中可能具有神经保护作用。
UNASSIGNED: Neuroinflammation plays an important part in the pathophysiology of sepsis-associated encephalopathy (SAE). Gut microbiota and gut brain axis are considered as important mediators in the development of neurological diseases. The aim of this study was to investigate the role of intestinal microbiota in sepsis-related brain injury and to explore the underlying mechanisms.
UNASSIGNED: Mouse model of SAE was established using cecal ligation and puncture (CLP). Based on the mouse mortality and the associated time of death, light SAE (LSAE) and severe SAE (SSAE) were classified. Fecal microbiota transplantation (FMT) was performed to verify the role of intestinal microbiota. Feces of mice in the two groups which collected before operation were sequenced for 16S and targeted short chain fatty acids.
UNASSIGNED: Intestinal microbiota from SSAE and LSAE mice displayed diverse functions. Interestingly, LSAE mice produced more butyric acid compared with SSAE mice. In the in vivo experiments, sodium butyrate (NaB) reduced the high oxidative stress levels in mice hippocampus and conferred a marked survival superiority to sepsis mice. In addition, NaB prevented the increase in intracellular reactive oxygen species (ROS) generation and inducible nitric-oxide synthase expression in LPS-stimulated primary microglia. The GPR109A/Nrf2/HO-1 signaling pathway was found to be involved in the activation of antioxidant response of primary microglia induced by sodium butyrate.
UNASSIGNED: Our findings indicate a crucial role of gut microbiota in the susceptibility to SAE. Butyrate, a metabolite of intestinal microbiota, may have a neuroprotective effect in the process of sepsis by GPR109A/Nrf2/HO-1 pathway.