3-羟基丁酸通过促进巨噬细胞M1向M2极化减轻脓毒症肝损伤  

3-Hydroxybutyrate alleviates septic liver injury by promoting macrophage polarization from M1 to M2

作　　者：胡敬娟 邓凡[1,2] 孙琦舜 闵玥 冯思远 伍玲 陈晓枫 刘克玄 Hu Jingjuan;Deng Fan;Sun Qishun;Min Yue;Feng Siyuan;Wu Ling;Chen Xiaofeng;Liu Kexuan(Department of Anesthesiology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong,China;The Key Laboratory of Precision Anesthesia&Perioperative Organ Protection,Guangzhou 510515,Guangdong,China)

机构地区：[1]南方医科大学南方医院麻醉科,广东广州510515 [2]广东省精准麻醉与围术期器官保护重点实验室,广东广州510515

出　　处：《生物医学转化》2024年第4期22-27,共6页Biomedical Transformation

基　　金：广东省基础与应用基础研究基金项目(2024A1515010534);国家自然科学基金重点项目(82330067);国家自然科学基金面上项目(82172141)。

摘　　要：目的 探讨代谢物3-羟基丁酸(3HB)对盲肠结扎穿刺(CLP)诱导的脓毒症小鼠模型的治疗效果及其机制。方法将雄性C57BL/6J小鼠分为Sham组、CLP组、CLP+3HB组。评估小鼠生存率、肝组织病理形态学损伤、血清中ALT和AST含量及肝组织炎症因子IL-1β和IL-6的mRNA表达。之后用氯磷酸脂质体清除巨噬细胞,探讨其在3HB治疗中的作用,将雄性C57BL/6J小鼠分为CLP组、CLP+3HB组、CLP+PBS-Lipro组、CLP+Clo-Lipro组和CLP+3HB+Clo-Lipro组。分析腹腔巨噬细胞M1和M2表型、肝损伤及炎症因子表达。结果 3HB显著提高脓毒症小鼠生存率,减轻肝损伤,降低ALT、AST及IL-1β和IL-6表达。3HB促进脓毒症小鼠腹腔巨噬细胞M1向M2极化,而清除巨噬细胞则加重脓毒症肝损伤,并逆转3HB的保护作用。结论 3HB通过促进巨噬细胞M1向M2极化,减轻脓毒症肝损伤,其作用依赖于巨噬细胞参与,该研究为临床上脓毒症肝损伤的治疗提供新的思路和潜在的干预策略。Objective To investigate the therapeutic effects and underlying mechanisms of the metabolite 3-hydroxybutyrate(3HB) in a cecal ligation and puncture(CLP)-induced sepsis model in mice.Methods Male C57BL/6J mice were divided into three groups:Sham,CLP,and CLP + 3HB groups.The survival rate,liver histopathological damage,serum levels of Alanine Transaminase(ALT) and Aspartate Aminotransferase(AST),and hepatic mRNA expression of inflammatory cytokines IL-1β and IL-6 were evaluated.Subsequently,macrophages were depleted using clodronate liposomes(Clo-Lipro) to explore their role in 3HB treatment.Male C57BL/6J mice were divided into five groups:CLP,CLP + 3HB,CLP + PBS-Lipro,CLP + Clo-Lipro,and CLP +3HB + Clo-Lipro.Peritoneal macrophage polarization(M1 and M2 phenotypes),liver injury,and inflammatory cytokine expression were analyzed.Results Treatment with 3HB significantly improved the survival rate of septic mice,alleviated liver injury,and reduced levels of ALT,AST,IL-1β,and IL-6.3HB promoted the polarization of macrophages from M1 to the M2 phenotype in septic mice,while macrophage depletion exacerbated liver injury in septic mice and reversed the protective effects of 3HB.Conclusion 3HB alleviates septic liver injury by promoting macrophage polarization from M1 to M2.This effect is dependent on the participation of macrophages,providing new insights and potential intervention strategies for the clinical treatment of septic liver injury.

关 键 词：脓毒症肝损伤 3-羟基丁酸 巨噬细胞极化 

分 类 号：R631[医药卫生—外科学]