摘要: |
脓毒症是宿主对感染反应失调引起的危及生命的器官功能障碍,其发病率和死亡率仍然居高不下,造成了严重的医疗负担。作为固有免疫和适应性免疫的重要组成部分,巨噬细胞具有高度的可塑性,可根据不同的环境刺激分化为M1促炎型和M2抗炎型,在脓毒症早期的过度炎症阶段和晚期的免疫抑制阶段均发挥着重要作用。M2巨噬细胞的代谢谱逐渐成为研究热点,其受多种酶和信号通路的调节,包括腺苷5'-单磷酸活化蛋白激酶、过氧化物酶体增殖物激活受体和蛋白激酶RNA样ER激酶等通路。这些关键的信号通路和酶通过调控葡萄糖、脂质和氨基酸代谢促进M2巨噬细胞极化并增强其抗炎功能,从而发挥脓毒症保护作用,可为脓毒症靶向治疗提供新的思路。 |
关键词: M2巨噬细胞 脓毒症 代谢重编程 极化 |
DOI:10.16781/j.CN31-2187/R.20240465 |
投稿时间:2024-06-30修订日期:2024-09-25 |
基金项目:国家自然科学基金(82272205). |
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M2 macrophage metabolism reprogramming in treating sepsis: research progress |
YANG Jinhui,JIANG Zhengyu,LI Bin,LIU Jiahao,BIAN Jinjun* |
(Department of Anesthesiology, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China *Corresponding author) |
Abstract: |
Sepsis refers to a life-threatening organ dysfunction caused by a dysregulated host response to infection, with persistently high morbidity and mortality, posing a significant healthcare burden. As integral components of innate and adaptive immunity, macrophages exhibit high plasticity and can differentiate into distinct phenotypes (M1 pro-inflammatory and M2 anti-inflammatory) in response to various environmental stimuli, playing crucial roles in both the hyperinflammatory phase and late immunosuppressive phase of sepsis. The metabolic profile of M2 macrophages has gradually become a research focus, and it is regulated by a variety of enzymes and signaling pathways, including adenosine 5'-monophosphate-activated protein kinase, peroxisome proliferator-activated receptor and protein kinase RNA-like ER kinase pathways. These pivotal signaling pathways and enzymes can promote the polarization of M2 macrophages and enhance their anti-inflammatory functions by modulating the metabolism of glucose, lipid, and amino acid, thereby conferring protective effects against sepsis and providing new ideas for the targeted treatment. |
Key words: M2 macrophages sepsis metabolism reprogramming polarization |