RESULTS: C57BL/6J mice are pretreated with saline or GA and subjected to sham or cecal ligation and puncture (CLP). The pathological alterations are assessed by hematoxylin and eosin staining as well as immunohistochemical staining. RNA sequencing is employed to analyze hepatic transcriptome modifications. The study finds that GA supplementation significantly ameliorates CLP-induced mortality, liver dysfunction, and inflammation. RNA sequencing reveals that 1324 genes are markedly differentially regulated in livers of saline- or GA-treated sham or CLP mice. Gene ontology analysis demonstrates that the differentially expressed genes regulated by GA are predominantly correlated with the immune system process, oxidation-reduction process, and inflammatory response. Furthermore, mitogen-activated protein kinase (MAPK) signaling is localized in the center of the GA-mediated pathway network. Notably, activation of MAPK by C16-PAF significantly blocks GA-mediated protective effects on hepatic injury, inflammation, as well as CCAAT/enhancer-binding protein-β (C/EBPβ) dependent extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling.
CONCLUSIONS: Therefore, this study indicates that GA may offer a promising therapeutic opportunity for sepsis-associated liver injury.
结果:用盐水或GA预处理C57BL/6J小鼠,并进行假手术或盲肠结扎和穿孔(CLP)。通过苏木精和伊红染色以及免疫组织化学染色评估病理改变。RNA测序用于分析肝转录组修饰。研究发现,补充GA可显着改善CLP诱导的死亡率,肝功能障碍,和炎症。RNA测序显示,在盐水或GA处理的假手术或CLP小鼠的肝脏中,有1324个基因受到显着差异调节。基因本体论分析表明,GA调控的差异表达基因主要与免疫系统过程相关,氧化还原过程,和炎症反应。此外,丝裂原活化蛋白激酶(MAPK)信号位于GA介导的途径网络的中心。值得注意的是,C16-PAF激活MAPK可显著阻断GA介导的肝损伤保护作用,炎症,以及CCAAT/增强子结合蛋白-β(C/EBPβ)依赖性细胞外信号调节激酶1/2(ERK1/2)和核因子-κB(NF-κB)信号。
结论:因此,这项研究表明,GA可能为脓毒症相关性肝损伤提供有希望的治疗机会.