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青蒿素酯通过LncRNA MALAT1/miR-155/Nrf2轴重塑巨噬细胞极化平衡缓解脓毒症肝损伤的研究进展. (2026). 环球医学研究, 3(5), 143-147. https://doi.org/10.62836/
Copyright (c) 2026 李玉红
This work is licensed under a Creative Commons Attribution 4.0 International License.
青蒿素酯通过LncRNA MALAT1/miR-155/Nrf2轴重塑巨噬细胞极化平衡缓解脓毒症肝损伤的研究进展
李玉红
浙江树人学院树兰国际医学院，树兰（杭州）医院手术麻醉科，浙江杭州
摘要：脓毒症性肝损伤的核心免疫病理环节在于肝脏巨噬细胞M1/M2极化平衡的丧失。青蒿素酯作为青蒿素的重要衍生物，兼具抗炎与免疫调节潜能，但其肝保护效应的分子框架尚待系统阐释。长链非编码RNA MALAT1作为巨噬细胞可塑性的上游调控节点，将青蒿素酯的药理作用与ceRNA网络联系起来。本综述以MALAT1/PTBP1/IFIH1轴与miR-155/Nrf2轴为双轨线索，系统梳理青蒿素酯经MALAT1相关网络重塑巨噬细胞极化平衡的分子逻辑。现有证据提示，青蒿素酯下调MALAT1，既削弱PTBP1/IFIH1依赖的M1极化驱动，又通过调整miR-155对Nrf2的抑制强度，协同激活Nrf2/HO-1抗氧化轴，在净效应上推动巨噬细胞由M1向M2偏移。这一“源头抑M1、下游促M2”的整合模型，为青蒿素酯靶向肝脏免疫微环境的脓毒症辅助治疗定位提供了理论依据。
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[2] Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study[J]. Lancet, 2020, 395(10219): 200-211.
[3] Ni L, Chen D, Zhao Y, et al. Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases. Front Immunol. 2024, 15: 1338125.
[4] Wang C, Ma C, Gong L, et al. Macrophage polarization and its role in liver disease[J]. Front Immunol, 2021, 12: 803037.
[5] 李同钦,董小荣,吕雅婷,等.青蒿琥酯治疗脓毒症的作用机制研究进展[J].2026,41(4):1146-1152.
[6] Zhao X, Huang X, Yang C, et al. Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling. Int J Mol Sci. 2022, 23(11): 6354.
[7] Jiang M, Lv Z, Huang Y, et al. Quercetin Alleviates Lipopolysaccharide-Induced Inflammatory Response in Bovine Mammary Epithelial Cells by Suppressing TLR4/NF-κB Signaling Pathway. Front Vet Sci. 2022, 9: 915726.
[8] Mountford S, Effenberger M, Noll-Puchta H, et al. Modulation of Liver Inflammation and Fibrosis by Interleukin-37. Front Immunol. 2021, 12: 603649.
[9] Zhou C. A multitherapy single-cell atlas reveals cell type-specific modulation in sepsis-induced liver injury. J Immunol. 2026, 215(2): vkaf351.
[10] Zhang Q, Liu J, Shen J, et al. Single-cell RNA sequencing reveals the effects of capsaicin in the treatment of sepsis-induced liver injury. MedComm (2020). 2023, 4(5): e395.
[11] Ji Y, Li X, Yao X, et al. Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies. Front Immunol. 2025, 16: 1732718.
[12] Guo Z, Wang L, Liu H, et al. Innate Immune Memory in Monocytes and Macrophages: The Potential Therapeutic Strategies for Atherosclerosis. Cells. 2022, 11(24): 4072.
[13] Chen Y, Yang L, Li X. Advances in Mesenchymal stem cells regulating macrophage polarization and treatment of sepsis-induced liver injury. Front. Immunol. 14: 1238972.
[14] 何泽英,朱宏泉.巨噬细胞极化在脓毒症及脓毒症相关肝损伤的作用[J].医学理论与实践,2024,37(22):3814-3816.
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[17] Yang Z, Xia H, Lai J, et al. Artesunate alleviates sepsis-induced liver injury by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis.Diagnostic Microbiology and Infectious Disease, 2024, 110(1): 10.
[18] Yuan Z, Huang Y, Sadikot RT. Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes HIV-1 Replication through Modulating microRNAs in Macrophages. J Virol. 2023, 97(6): e0005323.
[19] Wu H Y, Liu K, Zhang J L. LINC00240/miR-155 axis regulates function of trophoblasts and M2 macrophage polarization via modulating oxidative stress-induced pyroptosis in preeclampsia. Molecular medicine (Cambridge, Mass.), 2022, 28(1): 119.
[20] Yang ZB, Chen WW, Chen HP, et al. MiR-155 aggravated septic liver injury by oxidative stress-mediated ER stress and mitochondrial dysfunction via targeting Nrf-2. Exp Mol Pathol. 2018, 105(3): 387-394.
[21] Wei M, He J, Zhang Y, et al. Artesunate Targets MBL2 to Modulate the TLR4/NRF2/HO-1 Axis and Ameliorate Podophyllotoxin-Induced Liver Injury. Drug Des Devel Ther. 2026, 20: 608177.
[22] Kuang L, Zhang C, Li B, et al. Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p. International Journal of Nanomedicine. 2023, 18: 949-970.
[23] 张晓勇,周春祥.青蒿琥酯对大鼠肝Kupffer细胞分泌肝纤维化相关细胞因子的影响[J].安徽医学,2014,35(10):1437-1439.
[24] Wang L, He C. Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis.Front Immunol. 2022, 13: 967193.
[25] Liu Y, Zhang M, Wang T, et al. Reactive Oxygen Species in Asthma: Regulators of Macrophage Polarization and Therapeutic Implications: A Narrative Review. J Asthma Allergy. 2025, 18: 1129-1146.
[26] Chen JW, Liu CY, Li S, et al. Sepsis-associated liver injury: Mechanisms and potential therapeutic targets. World J Gastroenterol. 2024 Nov 14; 30(42): 4518-4522.
[27] 冯禹涵,陈金子,倪嘉威,等.脓毒症相关肝损伤的发病机制及治疗研究进展.国际麻醉学与复苏杂志,2026,47(8):728-734.
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[29] 程志杰,左瑞静,李欢欢,等.脓毒血症患者巨噬细胞外泌体miR-155对内皮细胞铁死亡的干预机制[J].昆明医科大学学报,2026,47(2):83-92.DOI:10.12259/j.issn.2095-610X. S20260209.
[30] Xie W, Lv L, Wang T, et al. The efficacy of artesunate in animal models of sepsis: a systematic review and meta-analysis. Front Pharmacol. 2026, 17: 1748083.