Department of Nutrition and Toxicology, School of Public Health, Hangzhou Normal University, Hangzhou, China, 311121.
Department of Cardiology, The First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College, Wuhu, Anhui, 241001, China.
Mol Nutr Food Res. 2024 Jun;68(11):e2400123. doi: 10.1002/mnfr.202400123. Epub 2024 May 29.
Liver injury is a major complication associated with sepsis. Together with others, the study has shown that gallic acid (GA) exerts anti-inflammatory and antioxidant effects in vivo. However, the role of GA in sepsis-mediated hepatic impairment and the underlying mechanisms remains to be elucidated.
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.
Therefore, this study indicates that GA may offer a promising therapeutic opportunity for sepsis-associated liver injury.
肝损伤是脓毒症的主要并发症。研究表明，没食子酸（GA）在体内具有抗炎和抗氧化作用。然而，GA 在脓毒症介导的肝损伤中的作用及其潜在机制仍有待阐明。
C57BL/6J 小鼠用生理盐水或 GA 预处理，然后进行假手术或盲肠结扎和穿刺（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。采用 RNA 测序分析肝转录组修饰。研究发现，GA 补充显著改善 CLP 诱导的死亡率、肝功能障碍和炎症。RNA 测序表明，盐水或 GA 处理的假手术或 CLP 小鼠的肝脏中 1324 个基因明显差异调节。基因本体分析表明，GA 调节的差异表达基因主要与免疫系统过程、氧化还原过程和炎症反应相关。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 显著阻断 GA 对肝损伤、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）信号的保护作用。
因此，本研究表明，GA 可能为脓毒症相关肝损伤提供有希望的治疗机会。
