目的 探讨细菌脂蛋白（BLP）训练巨噬细胞的代谢特征及柠康酸（Citra）保护内毒素血症小鼠的作用机制。 方法 用代谢组学分析BLP训练巨噬细胞感染金葡菌后的代谢变化；检测柠康酸抑菌及增强巨噬细胞吞杀菌和抗炎能力；评价柠康酸对内毒素血症小鼠生存率的影响。 结果 BLP训练显著增加巨噬细胞线粒体储备呼吸能力和糖酵解速率，升高糖酵解和TCA循环代谢物；抗炎代谢产物如衣康酸、柠康酸等增加。柠康酸能直接抑菌，增强巨噬细胞的吞、杀菌能力，并抑制细菌脂多糖（LPS）诱导的炎症因子水平。柠康酸显著提高内毒素血症小鼠7 d生存率，降低血清炎症因子及ALT、AST、BUN、Cr水平。 结论 BLP训练导致巨噬细胞代谢重编程，柠康酸通过抗炎、抗感染和抗器官损伤起保护作用。
Abstract
Objective To investigate the metabolic characteristics of macrophages trained by bacterial lipoprotein (BLP) and the protective effect of the upregulated metabolite citraconic acid against endotoxemia in mice and its underlying mechanism. Methods Using metabolomic profiling, we characterized the metabolic rewiring of BLP‑primed macrophages in response to S.aureus infection, and dissected the mechanisms by which citraconic acid exerts direct antibacterial effects, potentiates macrophage killing and clearance, and mitigates inflammatory cascades, ultimately conferring survival benefit in endotoxemic mice. Results BLP training significantly enhanced the mitochondrial spare respiratory capacity and glycolytic rate of macrophages, accompanied by elevated levels of glycolytic and tricarboxylic acid (TCA) cycle metabolites. Anti-inflammatory metabolites, including itaconic acid and citraconic acid, were also increased. citraconic acid exerted direct bacteriostatic effects, potentiated the phagocytic and bactericidal capacities of macrophages, and suppressed LPS-induced inflammatory cytokine production. Furthermore, citraconic acid markedly improved the 7-day survival rate in endotoxemic mice, and reduced serum levels of inflammatory cytokines, as well as ALT, AST, BUN, and Cr. Conclusions BLP training induces metabolic reprogramming in macrophages. Citraconic acid protects endotoxemic mice through mechanisms involving anti-inflammatory, anti-infective, and anti-organ damage activities.
关键词
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BLP训练 /
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内毒素血症 /
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巨噬细胞 /
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柠康酸
Key words
BLP training /
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Endotoxemia /
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Macrophages /
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Citraconic acid
中图分类号：
R392.11
R363.2
R364.5
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