鹅膏蕈中毒机制研究进展

陈 瑞云, 李 德忠
湖北民族大学附属恩施土家族苗族自治州中心医院

摘要


鹅膏蕈中毒是致死性野生蘑菇中毒的重要类型，其中α-amanitin是核心致死性毒素。其经典机制为特异性抑制RNA polymerase II，阻断mRNA转录和蛋白质合成，进而诱导肝细胞损伤和急性肝衰竭。近年来研究显示，其毒性机制已由单一转录抑制扩展至肝细胞摄取、氧化应激、自噬、凋亡及炎症小体激活等多层面损伤网络。OATP1B3介导的毒素摄取可解释其肝脏靶向毒性，AMPK-mTOR-ULK1、ROS/NF-κB/NLRP3等通路则参与肝损伤放大。目前临床治疗仍以支持治疗、阻断吸收、促进清除和肝移植评估为主，OATP1B3、NLRP3等靶点为后续特异性干预提供了新方向。

关键词


鹅膏蕈中毒；α-amanitin；RNA polymerase II；急性肝衰竭

全文:

PDF


参考


[1]Kayes T, Ho V. Amanita phalloides-Associated Liver Failure: Molecular Mechanisms and Management[J]. International Journal of Molecular Sciences, 2024, 25(23): 13028.

[2]Xue J, Lou X, Ning D, et al. Mechanism and treatment of α-amanitin poisoning[J]. Archives of Toxicology, 2023, 97(1): 121-131.

[3]Vetter J. Amanitins: The Most Poisonous Molecules of the Fungal World[J]. Molecules, 2023, 28(15): 5932.

[4]Brueckner F, Cramer P. Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation[J]. Nature Structural & Molecular Biology, 2008, 15(8): 811-818.

[5]Bushnell D A, Cramer P, Kornberg R D. Structural basis of transcription: α-Amanitin-RNA polymerase II cocrystal at 2.8 Å resolution[J/OL]. Proceedings of the National Academy of Sciences, 2002. DOI:10.1073/pnas.251664698.

[6]Letschert K, Faulstich H, Keller D, et al. Molecular Characterization and Inhibition of Amanitin Uptake into Human Hepatocytes[J/OL]. Toxicological Sciences, 2006. DOI:10.1093/toxsci/kfj141.

[7]Gu X, Zhang L, Sun W, et al. Autophagy Promotes α-Amanitin-Induced Apoptosis of Hepa1-6 Liver Cells[J]. Chemical Research in Toxicology, 2022, 35(3): 392-401.

[8]Xu Y, Wang S, Leung C K, et al. α-amanitin induces autophagy through AMPK-mTOR-ULK1 signaling pathway in hepatocytes[J]. Toxicology Letters, 2023, 383: 89-97.

[9]Zhao Z, Yi S, E H, 等. α-amanitin induce inflammatory response by activating ROS/NF-κB-NLRP3 signaling pathway in human hepatoma HepG2 cells[J]. Chemosphere, 2024, 364: 143157.

[10]Wang H, Zhang H, Miao L, et al. α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation[J]. Ecotoxicology and Environmental Safety, 2025, 290: 117749.


Refbacks

  • 当前没有refback。