ADAR1在脓毒症中的作用及研究进展
Role of ADAR1 in Sepsis and Research Progress
DOI: 10.12677/acm.2025.15113101, PDF,    国家自然科学基金支持
作者: 许亚楠, 王佩雯：西安医学院研究生工作部，陕西 西安；空军军医大学第一附属医院急诊科，陕西 西安；沈 括, 王仙琦, 吴 丹, 李俊杰*：空军军医大学第一附属医院急诊科，陕西 西安；郑 瑞：空军军医大学基础医学院免疫学教研室，陕西 西安
关键词: 脓毒症；ADAR1；细胞因子风暴；Sepsis； ADAR1； Cytokine Storm
摘要: 脓毒症(Sepsis)是指由于感染引起的宿主反应失调，其核心病理机制在于由细胞因子风暴所引起的免疫反应失衡而导致的危及生命的器官功能障碍。RNA特异性腺苷脱氨酶1 (ADAR1)，通过调控微小RNA (microRNA, miRNA)的生物合成和功能，进而调节细胞因子风暴及细胞死亡过程，从而在脓毒症病理进程中发挥重要作用。本篇文章旨在探讨ADAR1在脓毒症中的作用及研究进展，旨在为脓毒症的临床治疗探索新的视角与策略。
Abstract: Sepsis refers to a dysregulated host response to infection, with its core pathological mechanism being life-threatening organ dysfunction caused by an imbalanced immune response triggered by a cytokine storm. RNA-specific adenosine deaminase 1 (ADAR1) plays a crucial role in the pathophysiology of sepsis by regulating cytokine storms and cell death processes through its modulation of microRNA (miRNA) biosynthesis and function. The aim of this article is to discuss the role and research progress of ADAR1 in sepsis, with the aim of exploring new perspectives and strategies for the clinical treatment of sepsis.
文章引用：许亚楠, 沈括, 郑瑞, 王佩雯, 王仙琦, 吴丹, 李俊杰. ADAR1在脓毒症中的作用及研究进展[J]. 临床医学进展, 2025, 15(11): 322-329. https://doi.org/10.12677/acm.2025.15113101

参考文献

[1] Evans, L., Rhodes, A., Alhazzani, W., et al. (2021) Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine, 49, e1063-e1143.
[2] Huang, M., Cai, S. and Su, J. (2019) The Pathogenesis of Sepsis and Potential Therapeutic Targets. International Journal of Molecular Sciences, 20, Article 5376. [Google Scholar] [CrossRef] [PubMed]
[3] Lu, D., Lu, J., Liu, Q. and Zhang, Q. (2023) Emerging Role of the RNA-Editing Enzyme ADAR1 in Stem Cell Fate and Function. Biomarker Research, 11, Article No. 61. [Google Scholar] [CrossRef] [PubMed]
[4] 王仲, 魏捷, 朱华栋, 等. 中国脓毒症早期预防与阻断急诊专家共识[J]. 中国急救医学, 2020, 40(7): 577-588.
[5] 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]
[6] 王伊帆, 陈燕, 彭劲民, 等. 中国脓毒症流行病学的研究进展[J]. 中华重症医学电子杂志, 2023, 9(1): 89-94.
[7] Xie, J., Wang, H., Kang, Y., Zhou, L., Liu, Z., Qin, B., et al. (2020) The Epidemiology of Sepsis in Chinese ICUs: A National Cross-Sectional Survey. Critical Care Medicine, 48, e209-e218. [Google Scholar] [CrossRef] [PubMed]
[8] Grande, E., Grippo, F., Frova, L., Pantosti, A., Pezzotti, P. and Fedeli, U. (2019) The Increase of Sepsis-Related Mortality in Italy: A Nationwide Study, 2003-2015. European Journal of Clinical Microbiology & Infectious Diseases, 38, 1701-1708. [Google Scholar] [CrossRef] [PubMed]
[9] Fajgenbaum, D.C. and June, C.H. (2020) Cytokine Storm. New England Journal of Medicine, 383, 2255-2273. [Google Scholar] [CrossRef] [PubMed]
[10] Karki, R. and Kanneganti, T. (2021) The ‘Cytokine Storm’: Molecular Mechanisms and Therapeutic Prospects. Trends in Immunology, 42, 681-705. [Google Scholar] [CrossRef] [PubMed]
[11] Tang, X., Ji, T., Dong, J., Feng, H., Chen, F., Chen, X., et al. (2021) Pathogenesis and Treatment of Cytokine Storm Induced by Infectious Diseases. International Journal of Molecular Sciences, 22, Article 13009. [Google Scholar] [CrossRef] [PubMed]
[12] Kumar, V. (2020) Toll-Like Receptors in Sepsis-Associated Cytokine Storm and Their Endogenous Negative Regulators as Future Immunomodulatory Targets. International Immunopharmacology, 89, Article 107087. [Google Scholar] [CrossRef] [PubMed]
[13] Lelubre, C. and Vincent, J. (2018) Mechanisms and Treatment of Organ Failure in Sepsis. Nature Reviews Nephrology, 14, 417-427. [Google Scholar] [CrossRef] [PubMed]
[14] Wu, Z., Deng, J., Zhou, H., Tan, W., Lin, L. and Yang, J. (2022) Programmed Cell Death in Sepsis Associated Acute Kidney Injury. Frontiers in Medicine, 9, Article ID: 883028. [Google Scholar] [CrossRef] [PubMed]
[15] Nie, D., Chen, C., Li, Y. and Zeng, C. (2022) Disulfiram, an Aldehyde Dehydrogenase Inhibitor, Works as a Potent Drug against Sepsis and Cancer via Netosis, Pyroptosis, Apoptosis, Ferroptosis, and Cuproptosis. Blood Science, 4, 152-154. [Google Scholar] [CrossRef] [PubMed]
[16] Andreu-Ballester, J.C., Tormo-Calandín, C., Garcia-Ballesteros, C., Pérez-Griera, J., Amigó, V., Almela-Quilis, A., et al. (2013) Association of Gamadelta T Cells with Disease Severity and Mortality in Septic Patients. Clinical and Vaccine Immunology, 20, 738-746. [Google Scholar] [CrossRef] [PubMed]
[17] Lerolle, N., Nochy, D., Guérot, E., Bruneval, P., Fagon, J., Diehl, J., et al. (2010) Histopathology of Septic Shock Induced Acute Kidney Injury: Apoptosis and Leukocytic Infiltration. Intensive Care Medicine, 36, 471-478. [Google Scholar] [CrossRef] [PubMed]
[18] 周文琛, 何朝勇. 细胞死亡在脓毒症引起的肾损伤中的作用[J]. 药学研究, 2024, 43(1): 60-66.
[19] Xie, W., Hou, G., Wang, L., Wang, S. and Xiong, X. (2020) Astaxanthin Suppresses Lipopolysaccharide-Induced Myocardial Injury by Regulating MAPK and PI3K/Akt/mTOR/GSK3β Signaling. Molecular Medicine Reports, 22, 3338-3346. [Google Scholar] [CrossRef] [PubMed]
[20] Qu, M., Wang, Y., Qiu, Z., Zhu, S., Guo, K., Chen, W., et al. (2022) Necroptosis, Pyroptosis, Ferroptosis in Sepsis and Treatment. Shock, 57, 161-171. [Google Scholar] [CrossRef] [PubMed]
[21] 陈祝桂, 彭志勇, 张智豪, 等. 不同浓度脂多糖对脓毒症急性肺损伤肺上皮细胞坏死性凋亡和线粒体自噬的影响[J]. 中华实用诊断与治疗杂志, 2020, 34(4): 330-333.
[22] Guo, R., Wang, H. and Cui, N. (2021) Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis. Mediators of Inflammation, 2021, Article 9925059. [Google Scholar] [CrossRef] [PubMed]
[23] 石颖慧, 牛文凯, 苑鑫. 脓毒症中细胞因子风暴的机制及治疗研究进展[J]. 军事医学, 2023, 47(8): 626-630.
[24] 陈怡慧, 董鹏, 张喜洋, 等. 促炎细胞因子在脓毒症中作用的研究进展[J]. 中华危重病急救医学, 2023, 35(2): 212-216.
[25] 刘爽, 马文成, 张贤英, 等. 过敏性鼻炎患者血清IL-8, IL-22及TNF-α水平的变化及其与病情严重程度的关系研究[J]. 现代生物医学进展, 2020, 20(9): 1716-1719, 1777.
[26] 赵乙汜, 张苜, 余应喜. 血清白细胞介素联合监测在脓毒症严重程度及预后评估中的作用研究[J]. 重庆医科大学学报, 2020, 45(8): 1198-1203.
[27] 刘向龙, 陈剑明, 杨玲, 等. 血清TNF-α、SAA在脓毒症休克预后评估中的价值分析[J]. 重庆医学, 2023, 52(3): 374-378.
[28] Bass, B.L. (2002) RNA Editing by Adenosine Deaminases That Act on RNA. Annual Review of Biochemistry, 71, 817-846. [Google Scholar] [CrossRef] [PubMed]
[29] Nishikura, K. (2010) Functions and Regulation of RNA Editing by ADAR Deaminases. Annual Review of Biochemistry, 79, 321-349. [Google Scholar] [CrossRef] [PubMed]
[30] Hayashi, M. and Suzuki, T. (2013) Dyschromatosis Symmetrica Hereditaria. The Journal of Dermatology, 40, 336-343. [Google Scholar] [CrossRef] [PubMed]
[31] Poulsen, H., Nilsson, J., Damgaard, C.K., Egebjerg, J. and Kjems, J. (2001) CRM1 Mediates the Export of ADAR1 through a Nuclear Export Signal within the Z-DNA Binding Domain. Molecular and Cellular Biology, 21, 7862-7871. [Google Scholar] [CrossRef] [PubMed]
[32] Li, L., Qian, G., Zuo, Y., Yuan, Y., Cheng, Q., Guo, T., et al. (2016) Ubiquitin-Dependent Turnover of Adenosine Deaminase Acting on RNA 1 (ADAR1) Is Required for Efficient Antiviral Activity of Type I Interferon. Journal of Biological Chemistry, 291, 24974-24985. [Google Scholar] [CrossRef] [PubMed]
[33] Song, B., Shiromoto, Y., Minakuchi, M. and Nishikura, K. (2021) The Role of RNA Editing Enzyme ADAR1 in Human Disease. WIREs RNA, 13, e1665. [Google Scholar] [CrossRef] [PubMed]
[34] Yang, W., Chendrimada, T.P., Wang, Q., Higuchi, M., Seeburg, P.H., Shiekhattar, R., et al. (2006) Modulation of MicroRNA Processing and Expression through RNA Editing by ADAR Deaminases. Nature Structural & Molecular Biology, 13, 13-21. [Google Scholar] [CrossRef] [PubMed]
[35] Wang, H.F., Li, Y., Wang, Y.Q., et al. (2019) MicroRNA-494-3p Alleviates Inflammatory Response in Sepsis by Targeting TLR6. European Review for Medical and Pharmacological Sciences, 23, 2971-2977.
[36] Walkley, C.R. and Li, J.B. (2017) Rewriting the Transcriptome: Adenosine-To-Inosine RNA Editing by Adars. Genome Biology, 18, Article no. 205. [Google Scholar] [CrossRef] [PubMed]
[37] Ota, H., Sakurai, M., Gupta, R., Valente, L., Wulff, B., Ariyoshi, K., et al. (2013) ADAR1 Forms a Complex with Dicer to Promote MicroRNA Processing and RNA-Induced Gene Silencing. Cell, 153, 575-589. [Google Scholar] [CrossRef] [PubMed]
[38] Zhang, X., Gao, X., Hu, J., Xie, Y., Zuo, Y., Xu, H., et al. (2019) Adar1p150 Forms a Complex with Dicer to Promote MiRNA-222 Activity and Regulate PTEN Expression in CVB3-Induced Viral Myocarditis. International Journal of Molecular Sciences, 20, Article 407. [Google Scholar] [CrossRef] [PubMed]
[39] Li, B. and Xie, X. (2022) A20 (TNFAIP3) Alleviates Viral Myocarditis through ADAR1/miR-1a-3p-Dependent Regulation. BMC Cardiovascular Disorders, 22, Article No. 10. [Google Scholar] [CrossRef] [PubMed]
[40] Cai, D., Sun, C., Murashita, T., Que, X. and Chen, S. (2023) ADAR1 Non-Editing Function in Macrophage Activation and Abdominal Aortic Aneurysm. Circulation Research, 132, e78-e93. [Google Scholar] [CrossRef] [PubMed]
[41] Díaz-Piña, G., Ordoñez-Razo, R.M., Montes, E., Páramo, I., Becerril, C., Salgado, A., et al. (2018) The Role of ADAR1 and ADAR2 in the Regulation of MiRNA-21 in Idiopathic Pulmonary Fibrosis. Lung, 196, 393-400. [Google Scholar] [CrossRef] [PubMed]
[42] 刘善收. 脓毒症早期单核巨噬细胞凋亡与预后相关性及调控机制的研究[D]: [博士学位论文]. 西安: 中国人民解放军空军军医大学, 2023.
[43] Li, J., Xie, J., Liu, S., Li, X., Zhang, D., Wang, X., et al. (2018) ADAR1 Attenuates Allogeneic Graft Rejection by Suppressing miR-21 Biogenesis in Macrophages and Promoting M2 Polarization. The FASEB Journal, 32, 5162-5173. [Google Scholar] [CrossRef] [PubMed]
[44] Shangxun, Z., Junjie, L., Wei, Z., Yutong, W., Wenyuan, J., Shanshou, L., et al. (2020) ADAR1 Alleviates Inflammation in a Murine Sepsis Model via the ADAR1-miR-30a-SOCS3 Axis. Mediators of Inflammation, 2020, Article ID: 9607535. [Google Scholar] [CrossRef] [PubMed]
[45] Zhao, X., Xie, J., Duan, C., Wang, L., Si, Y., Liu, S., et al. (2024) ADAR1 Protects Pulmonary Macrophages from Sepsis-Induced Pyroptosis and Lung Injury through miR-21/a20 Signaling. International Journal of Biological Sciences, 20, 464-485. [Google Scholar] [CrossRef] [PubMed]
[46] Liu, S., Xie, J., Duan, C., Zhao, X., Feng, Z., Dai, Z., et al. (2024) ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-Induced Liver Injury through miR-122/BCL2A1 Signaling. Journal of Clinical and Translational Hepatology, 12, 134-150. [Google Scholar] [CrossRef] [PubMed]

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