乳酸是细胞糖酵解的主要代谢产物,在能量供给和信号转导方面发挥重要作用。 乳酸在多种疾病的发生、发展中发挥重 要作用,还通过抑制免疫细胞、营造免疫抑制性微环境等途径促进多类肿瘤的进展。 2019 年首次报道的以乳酸为底物的乳酸化修饰 参与基因转录调控及蛋白质结构和功能的调节,这为乳酸在生理病理过程中的作用提供了新的见解。 本综述回顾性分析了乳酸化 修饰的相关研究,并总结了乳酸化修饰的调控机制,组蛋白乳酸化位点及其在干细胞和胚胎发育、炎症、肿瘤等疾病发展过程中的调 控作用,和各非组蛋白乳酸化位点及其在生理病理中的作用。 最后,我们总结了部分乳酸化修饰研究中尚未解决的问题。 乳酸化修 饰参与多种疾病的发生发展,靶向乳酸化或许能作为临床治疗相关疾病的策略之一。 然而,目前乳酸化修饰的调控机制及其在疾病 发生发展中的调节作用尚不完全清晰,靶向乳酸化修饰仍处于理论阶段,还需行进一步机制探索,开展临床前研究,以期为治疗乳酸 化修饰相关疾病提供新思路。

Lactic acid is the main metabolic product of glycolysis and plays a vital role in energy supply and signal transduction. Lactate plays an important role in the development of a variety of diseases and promotes the progression of several types of tumours by inhibiting immune cells and creating an immunosuppressive microenvironment. The role of lactylation derived from lactic acid in gene transcription regulation and the modulation of protein structure and function was first reported in 2019 providing new insights into the role of lactate in physiological and pathological processes. This review retrospectively analyzes the published research on lactylation and summarizes the regulatory mechanisms of lactylation the histone lactylation sites and their regulatory role in the physiological and pathological processes of stem cells and embryonic development inflammation tumors and other diseases and the non-histone lactylation sites and their roles in physiopathology. Finally we summarise some of the unresolved issues in lactylation research. Lactylation is involved in the development of various diseases and targeting lactylation may serve as one of the strategies for clinical treatment of related diseases. However the regulatory mechanism of lactylation and its physiological regulatory role in the occurrence and development of diseases remains unclear and targeting lactylation is still in the theoretical stage. Further exploration of the mechanism and preclinical studies is needed to provide new view for the treatment of lactylation-related diseases.