组蛋白乳酸化调节脓毒症代谢

Metabolic regulation of sepsis by histone lactylation

表观遗传调控在脓毒症发病机制中发挥重要作用,特别是在脓毒症免疫抑制阶段,广泛的组蛋白修饰改变了组蛋白之间及其与DNA的关系,进而可影响多器官功能障碍。组蛋白乳酸化是表观遗传修饰方式之一,作为近几年表观遗传修饰的研究热点,其在炎症、糖尿病、癌症等病理机制方面均有重要作用。脓毒症的病理生理机制尚不完全清楚,但已有研究表明表观遗传参与调节脓毒症的炎症反应,乳酸作为组蛋白乳酸化修饰的底物可调控脓毒症免疫细胞的功能。将代谢调节同免疫治疗相结合,在脓毒症临床治疗中具有很大的潜力。因此,本文对组蛋白乳酸化修饰及其对脓毒症的代谢影响进行了综述,并结合代谢重编程的作用靶点总结了可能的抗脓毒症治疗途径。

Epigenetic regulation plays an important role in the pathogenesis of sepsis,especially during the immunosuppressive phase of sepsis,where extensive histone modifications alter the relationship between histones and their relationship with DNA,which in turn can affect multi-organ dysfunction.Histone lactylation is one of the epigenetic modification research.As a research hotspot of epigenetic modification in recent years,it plays an important role in the pathological mechanisms of inflammation,diabetes,cancer.The pathophysiological mechanisms of sepsis are not fully understood,but it has been shown that epigenetic involvement in regulating the inflammatory response in sepsis and lactate as a substrate for histone lactonization modification can modulate immune cell function in sepsis.Combining metabolic modulation with immunotherapy has great potential in the clinical treatment of sepsis.Therefore,we have reviewed histone lactylation modifications and their metabolic effects on sepsis.Combined with the targets of metabolic reprogramming,possible anti-sepsis therapeutic pathways are summarized.