Zhang Junli, Li Na, Hu Xiaoyu
Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
J Immunol Res. 2024 Dec 24;2024:5891381. doi: 10.1155/jimr/5891381. eCollection 2024.
Acute liver failure (ALF) is a fulminant clinical syndrome that usually leads to multiple organ failure and high mortality. Macrophages play a crucial role in the initiation, development, and recovery of ALF. Targeting macrophages through immunotherapy holds significant promise as a therapeutic strategy. These cells exhibit remarkable plasticity, enabling them to differentiate into various subtypes based on changes in their surrounding microenvironment. M1-type macrophages are associated with a pro-inflammatory phenotype and primarily rely predominantly on glycolysis. In contrast, M2-type macrophages, which are characterized by anti-inflammatory phenotype, predominantly obtain their energy from oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Shifting macrophage metabolism from glycolysis to OXPHOS inhibits M1 macrophage activation and promotes M2 macrophage activation, thereby exerting anti-inflammatory and reparative effects. This study elucidates the relationship between macrophage activation and glucose metabolism reprograming from an immunometabolism perspective. A comprehensive literature review revealed that several signaling pathways may regulate macrophage polarization through energy metabolism, including phosphatidyl-inositol 3-kinase/protein kinase B (PI3K/AKT), mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1 (HIF-1), nuclear factor-B (NF-B), and AMP-activated protein kinase (AMPK), which exhibit crosstalk with one another. Additionally, we systematically reviewed several traditional Chinese medicine (TCM) monomers that can modulate glucose metabolism reprograming and influence the polarization states of M1 and M2 macrophages. This review aimed to provide valuable insights that could contribute to the development of new therapies or drugs for ALF.
急性肝衰竭（ALF）是一种暴发性临床综合征，通常会导致多器官衰竭和高死亡率。巨噬细胞在ALF的起始、发展和恢复过程中起着关键作用。通过免疫疗法靶向巨噬细胞作为一种治疗策略具有巨大的潜力。这些细胞表现出显著的可塑性，使其能够根据周围微环境的变化分化为各种亚型。M1型巨噬细胞与促炎表型相关，主要依赖糖酵解。相比之下，以抗炎表型为特征的M2型巨噬细胞主要通过氧化磷酸化（OXPHOS）和脂肪酸氧化（FAO）获取能量。将巨噬细胞代谢从糖酵解转变为OXPHOS可抑制M1巨噬细胞的激活并促进M2巨噬细胞的激活，从而发挥抗炎和修复作用。本研究从免疫代谢的角度阐明了巨噬细胞激活与葡萄糖代谢重编程之间的关系。一项全面的文献综述表明，几种信号通路可能通过能量代谢调节巨噬细胞极化，包括磷脂酰肌醇3激酶/蛋白激酶B（PI3K/AKT）、雷帕霉素靶蛋白（mTOR）/缺氧诱导因子1（HIF-1）、核因子-κB（NF-κB）和AMP激活的蛋白激酶（AMPK），它们之间存在相互作用。此外，我们系统地综述了几种能够调节葡萄糖代谢重编程并影响M1和M2巨噬细胞极化状态的中药单体。本综述旨在提供有价值的见解，为开发治疗ALF的新疗法或药物做出贡献。
