乳酸化在脓毒症相关器官损伤中的机制研究
Study on the Mechanism of Lactylation in Organ Damage Related to Sepsis
DOI: 10.12677/acm.2025.15102991, PDF,    科研立项经费支持
作者: 李百远:延安大学附属医院重症医学科,陕西 延安
关键词: 脓毒症乳酸化器官损伤Sepsis Lactylation Organ Damage
摘要: 脓毒症作为严重困扰人类健康的疾病,具有致死率高,预后差等特点。因脓毒症病理生理机制复杂,并且易合并多脏器损伤,目前仍缺乏可行的治疗方法来提高患者生存率,因此,了解脓毒症中器官损伤的潜在机制对于制定有效的治疗策略至关重要。研究表明,乳酸化修饰通过调控免疫反应、炎症过程以及细胞信号通路等,与脓毒症的严重程度和预后密切相关。本文就乳酸化在脓毒症诱导的相关脏器损伤中的研究作一综述,旨在为脓毒症的治疗提供临床思路。
Abstract: As a disease that seriously plagues human health, sepsis has the characteristics of high mortality and poor prognosis. Because the pathophysiological mechanism of sepsis is complex and prone to multiple organ damage, there is still a lack of feasible treatment methods to improve patient survival. Therefore, understanding the underlying mechanisms of organ damage in sepsis is crucial to formulating effective treatment strategies. Studies have shown that lactylation is closely related to the severity and prognosis of sepsis by regulating immune responses, inflammatory processes, and cellular signaling pathways. This paper reviews the research on lactylation in related organ damage induced by sepsis, aiming to provide clinical ideas for the treatment of sepsis.
文章引用:李百远. 乳酸化在脓毒症相关器官损伤中的机制研究[J]. 临床医学进展, 2025, 15(10): 2127-2134. https://doi.org/10.12677/acm.2025.15102991

参考文献

[1] Rudd, K.E., Johnson, S.C., Agesa, K.M., Shackelford, K.A., Tsoi, D., Kievlan, D.R., et al. (2020) Global, Regional, and National Sepsis Incidence and Mortality, 1990-2017: Analysis for the Global Burden of Disease Study. The Lancet, 395, 200-211. [Google Scholar] [CrossRef] [PubMed]
[2] Singer, M., Deutschman, C.S., Seymour, C.W., Shankar-Hari, M., Annane, D., Bauer, M., et al. (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315, 801-810. [Google Scholar] [CrossRef] [PubMed]
[3] Evans L, Rhodes A, Alhazzani W, et al. (2021) Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Medicine, 47, 1181‐1247.
[4] Zhang, D., Tang, Z., Huang, H., Zhou, G., Cui, C., Weng, Y., et al. (2019) Metabolic Regulation of Gene Expression by Histone Lactylation. Nature, 574, 575-580. [Google Scholar] [CrossRef] [PubMed]
[5] Fang, C., Ren, P., Bian, G., Wang, J., Bai, J., Huang, J., et al. (2023) Enhancing Spns2/S1P in Macrophages Alleviates Hyperinflammation and Prevents Immunosuppression in Sepsis. EMBO Reports, 24, e56635. [Google Scholar] [CrossRef] [PubMed]
[6] Sangsuwan, R., Thuamsang, B., Pacifici, N., Tachachartvanich, P., Murphy, D., Ram, A., et al. (2025) Identification of Signaling Networks Associated with Lactate Modulation of Macrophages and Dendritic Cells. Heliyon, 11, e42098. [Google Scholar] [CrossRef] [PubMed]
[7] Wang, Y., Wei, A., Su, Z., Shi, Y., Li, X. and He, L. (2025) Characterization of Lactylation-Based Phenotypes and Molecular Biomarkers in Sepsis-Associated Acute Respiratory Distress Syndrome. Scientific Reports, 15, Article No. 13831. [Google Scholar] [CrossRef] [PubMed]
[8] Sun, Z., Song, Y., Li, J., Li, Y., Yu, Y. and Wang, X. (2023) Potential Biomarker for Diagnosis and Therapy of Sepsis: Lactylation. Immunity, Inflammation and Disease, 11, e1042. [Google Scholar] [CrossRef] [PubMed]
[9] Liu, S., Yang, T., Jiang, Q., Zhang, L., Shi, X., Liu, X., et al. (2024) Lactate and Lactylation in Sepsis: A Comprehensive Review. Journal of Inflammation Research, 17, 4405-4417. [Google Scholar] [CrossRef] [PubMed]
[10] Gong, F., Zheng, X., Xu, W., Xie, R., Liu, W., Pei, L., et al. (2025) H3k14la Drives Endothelial Dysfunction in Sepsis‐induced ARDS by Promoting SLC40A1/Transferrin-Mediated Ferroptosis. MedComm, 6, e70049. [Google Scholar] [CrossRef] [PubMed]
[11] Ma, N., Wang, L., Meng, M., Wang, Y., Huo, R., Chang, G., et al. (2025) D-Sodium Lactate Promotes the Activation of Nf-κB Signaling Pathway Induced by Lipopolysaccharide via Histone Lactylation in Bovine Mammary Epithelial Cells. Microbial Pathogenesis, 199, Article 107198. [Google Scholar] [CrossRef] [PubMed]
[12] Li, J., Shi, X., Xu, J., Wang, K., Hou, F., Luan, X., et al. (2025) Aldehyde Dehydrogenase 2 Lactylation Aggravates Mitochondrial Dysfunction by Disrupting PHB2 Mediated Mitophagy in Acute Kidney Injury. Advanced Science, 12, e2411943. [Google Scholar] [CrossRef] [PubMed]
[13] Li, S., Shen, Y., Wang, C., Yang, J., Chen, M. and Hu, Y. (2024) Exploring the Prognostic and Diagnostic Value of Lactylation-Related Genes in Sepsis. Scientific Reports, 14, Article No. 23130. [Google Scholar] [CrossRef] [PubMed]
[14] Qiao, J., Tan, Y., Liu, H., Yang, B., Zhang, Q., Liu, Q., et al. (2024) Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis-Associated Acute Kidney Injury. Advanced Science, 11, e2307216. [Google Scholar] [CrossRef] [PubMed]
[15] Wu, D., Spencer, C.B., Ortoga, L., Zhang, H. and Miao, C. (2024) Histone Lactylation-Regulated METTL3 Promotes Ferroptosis via m6A-Modification on ACSL4 in Sepsis-Associated Lung Injury. Redox Biology, 74, Article 103194. [Google Scholar] [CrossRef] [PubMed]
[16] Gong, T., Wang, Q., Loughran, P.A., Li, Y., Scott, M.J., Billiar, T.R., et al. (2024) Mechanism of Lactic Acidemia-Promoted Pulmonary Endothelial Cells Death in Sepsis: Role for CIRP-ZBP1-Panoptosis Pathway. Military Medical Research, 11, Article No. 71. [Google Scholar] [CrossRef] [PubMed]
[17] Li, Z., Bu, Y., Wang, C., Yu, Y., Han, L., Liu, C., et al. (2025) Extracellular Vesicle-Packaged GBP2 from Macrophages Aggravates Sepsis-Induced Acute Lung Injury by Promoting Ferroptosis in Pulmonary Vascular Endothelial Cells. Redox Biology, 82, Article 103614. [Google Scholar] [CrossRef] [PubMed]
[18] Lu, Z., Fang, P., Li, S., Xia, D., Zhang, J., Wu, X., et al. (2024) Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis-Induced Acute Lung Injury. Advanced Science, 12, e2407064. [Google Scholar] [CrossRef] [PubMed]
[19] An, S., Yao, Y., Hu, H., Wu, J., Li, J., Li, L., et al. (2023) PDHA1 Hyperacetylation-Mediated Lactate Overproduction Promotes Sepsis-Induced Acute Kidney Injury via Fis1 Lactylation. Cell Death & Disease, 14, Article No. 457. [Google Scholar] [CrossRef] [PubMed]
[20] Wu, Z., Liu, W.Q., Tang, L., Yuan, Q., Li, Y., Hu, H., et al. (2024) Lactate-Mitochondrial Crosstalk: A New Direction in the Treatment of Sepsis-Induced Acute Kidney Injury. Cell Biology International, 48, 1621-1624. [Google Scholar] [CrossRef] [PubMed]
[21] Li, L. and Lu, Y. (2021) The Regulatory Role of High-Mobility Group Protein 1 in Sepsis-Related Immunity. Frontiers in Immunology, 11, Article ID: 601815. [Google Scholar] [CrossRef] [PubMed]
[22] Wei, S., Dai, Z., Wu, L., Xiang, Z., Yang, X., Jiang, L., et al. (2025) Lactate-Induced Macrophage HMGB1 Lactylation Promotes Neutrophil Extracellular Trap Formation in Sepsis-Associated Acute Kidney Injury. Cell Biology and Toxicology, 41, Article No. 78. [Google Scholar] [CrossRef] [PubMed]
[23] Zuo, L., Prather, E.R., Stetskiv, M., Garrison, D.E., Meade, J.R., Peace, T.I., et al. (2019) Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments. International Journal of Molecular Sciences, 20, Article 4472. [Google Scholar] [CrossRef] [PubMed]
[24] Jang, H.M., Lee, J.Y., An, H.S., Ahn, Y.J., Jeong, E.A., Shin, H.J., et al. (2022) LCN2 Deficiency Ameliorates Doxorubicin-Induced Cardiomyopathy in Mice. Biochemical and Biophysical Research Communications, 588, 8-14. [Google Scholar] [CrossRef] [PubMed]
[25] Huang, Y., Zhang, N., Xie, C., You, Y., Guo, L., Ye, F., et al. (2022) Lipocalin-2 in Neutrophils Induces Ferroptosis in Septic Cardiac Dysfunction via Increasing Labile Iron Pool of Cardiomyocytes. Frontiers in Cardiovascular Medicine, 9, Article ID: 922534. [Google Scholar] [CrossRef] [PubMed]
[26] Li, Y., Li, L., Zhang, Y., Yun, Q., Du, R., Ye, H., et al. (2025) Lipocalin-2 Silencing Alleviates Sepsis-Induced Liver Injury through Inhibition of Ferroptosis. Annals of Hepatology, 30, Article 101756. [Google Scholar] [CrossRef] [PubMed]
[27] Hu, S., Yang, Z., Li, L., Yan, Q., Hu, Y., Zhou, F., et al. (2024) Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages. Molecules, 29, Article 236. [Google Scholar] [CrossRef] [PubMed]
[28] He, L., Yin, R., Hang, W., Han, J., Chen, J., Wen, B., et al. (2024) Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia through TNF Pathway. Biomedicines, 12, Article 2371. [Google Scholar] [CrossRef] [PubMed]
[29] Chung, H., Wickel, J., Hahn, N., Mein, N., Schwarzbrunn, M., Koch, P., et al. (2023) Microglia Mediate Neurocognitive Deficits by Eliminating C1q-Tagged Synapses in Sepsis-Associated Encephalopathy. Science Advances, 9, eabq7806. [Google Scholar] [CrossRef] [PubMed]
[30] Chen, L., Luo, S., Liu, T., Shuai, Z., Song, Y., Yang, Q., et al. (2025) Growth Differentiation Factor 15 Aggravates Sepsis-Induced Cognitive and Memory Impairments by Promoting Microglial Inflammatory Responses and Phagocytosis. Journal of Neuroinflammation, 22, Article No. 44. [Google Scholar] [CrossRef] [PubMed]
[31] Gao, S., Shen, R., Li, J., Jiang, Y., Sun, H., Wu, X., et al. (2024) N-Acetyltransferase 10 Mediates Cognitive Dysfunction through the Acetylation of Gababr1 mRNA in Sepsis-Associated Encephalopathy. Proceedings of the National Academy of Sciences, 121, e2410564121. [Google Scholar] [CrossRef] [PubMed]
[32] Li, H., Liu, Q., Zhu, C., Sun, X., Sun, C., Yu, C., et al. (2023) β-Nicotinamide Mononucleotide Activates NAD+/SIRT1 Pathway and Attenuates Inflammatory and Oxidative Responses in the Hippocampus Regions of Septic Mice. Redox Biology, 63, Article 102745. [Google Scholar] [CrossRef] [PubMed]
[33] Liao, Y., Niu, L., Ling, J., Cui, Y., Huang, Z., Xu, J., et al. (2025) Turning Sour into Sweet: Lactylation Modification as a Promising Target in Cardiovascular Health. Metabolism, 168, Article 156234. [Google Scholar] [CrossRef] [PubMed]
[34] Shi, Y., He, L., Ni, J., Zhou, Y., Yu, X., Du, Y., et al. (2025) Myeloid Deficiency of Z-DNA Binding Protein 1 Restricts Septic Cardiomyopathy via Promoting Macrophage Polarisation Towards the M2-Subtype. Clinical and Translational Medicine, 15, e70315. [Google Scholar] [CrossRef] [PubMed]
[35] Wang, F., Xue, P., Wang, J., Liu, Y., Han, X. and Xing, J. (2025) Esmolol Upregulates the α7 nAChR/STAT3/NF-κB Pathway by Decreasing the Ubiquitin and Increasing the ChAT+CD4+ T Lymphocyte to Alleviate Inflammation in Septic Cardiomyopathy. International Immunopharmacology, 148, Article 114043. [Google Scholar] [CrossRef] [PubMed]
[36] Li, Y., Zhang, X., Jiang, G., Min, X., Kong, Q., Liu, L., et al. (2025) Downregulation of HSPA12A Protects Heart against Sepsis through Suppressing mTOR-Mediated Inflammatory Response in Cardiomyocytes. International Immunopharmacology, 145, Article 113721. [Google Scholar] [CrossRef] [PubMed]
[37] Zhang, Y., Liu, Y., Xie, Z., Liu, Q., Zhuang, Y., Xie, W., et al. (2022) Inhibition of PFKFB Preserves Intestinal Barrier Function in Sepsis by Inhibiting NLRP3/GSDMD. Oxidative Medicine and Cellular Longevity, 2022, Article ID: 8704016. [Google Scholar] [CrossRef] [PubMed]
[38] Zhu, L., Dou, Z., Wu, W., Hou, Q., Wang, S., Yuan, Z., et al. (2023) Ghrelin/GHSR Axis Induced M2 Macrophage and Alleviated Intestinal Barrier Dysfunction in a Sepsis Rat Model by Inactivating E2F1/NF-κB Signaling. Canadian Journal of Gastroenterology and Hepatology, 2023, Article ID: 1629777. [Google Scholar] [CrossRef] [PubMed]
[39] Wu, R., Xu, J., Zeng, H., Fan, Y., Li, H., Peng, T., et al. (2024) Golden Bifid Treatment Regulates Gut Microbiota and Serum Metabolites to Improve Myocardial Dysfunction in Cecal Ligation and Puncture-Induced Sepsis Mice. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1870, Article 167049. [Google Scholar] [CrossRef] [PubMed]
[40] Chen, Y., Sun, K., Qi, Y., Tang, J., Zhu, H. and Wang, Z. (2024) L-Valine Derived from the Gut Microbiota Protects Sepsis-Induced Intestinal Injury and Negatively Correlates with the Severity of Sepsis. Frontiers in Immunology, 15, Article ID: 1424332. [Google Scholar] [CrossRef] [PubMed]
[41] Cheng, L., Feng, B., Xie, C., Chen, C. and Guo, L. (2025) Overexpression of miR-20a Targeting DUSP3 Inhibits OCLN Ubiquitination Levels and Alleviates Sepsis Induced Intestinal Barrier Dysfunction. In Vitro Cellular & Developmental Biology-Animal, 61, 459-471. [Google Scholar] [CrossRef] [PubMed]
[42] Cao, Y., Qiao, Y., Wang, Z., Chen, Q., Qi, Y., Lu, Z., et al. (2023) The Polo-Like Kinase 1-Mammalian Target of Rapamycin Axis Regulates Autophagy to Prevent Intestinal Barrier Dysfunction during Sepsis. The American Journal of Pathology, 193, 296-312. [Google Scholar] [CrossRef] [PubMed]