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α-鹅膏毒肽诱导肝细胞毒性作用机制的研究进展

许悦 王婵 林纾丞 张慧洁 澹忆 张树威 曾晓锋 李桢

许悦, 王婵, 林纾丞, 张慧洁, 澹忆, 张树威, 曾晓锋, 李桢. α-鹅膏毒肽诱导肝细胞毒性作用机制的研究进展[J]. 昆明医科大学学报, 2022, 43(12): 153-158. doi: 10.12259/j.issn.2095-610X.S20221228
引用本文: 许悦, 王婵, 林纾丞, 张慧洁, 澹忆, 张树威, 曾晓锋, 李桢. α-鹅膏毒肽诱导肝细胞毒性作用机制的研究进展[J]. 昆明医科大学学报, 2022, 43(12): 153-158. doi: 10.12259/j.issn.2095-610X.S20221228
Yue XU, Chan WANG, Shucheng LIN, Huijie ZHANG, Yi TAN, Shuwei ZHANG, Xiaofeng ZENG, Zhen LI. Advances in the Mechanism of Hepatotoxic Effects Induced by α-amanitin[J]. Journal of Kunming Medical University, 2022, 43(12): 153-158. doi: 10.12259/j.issn.2095-610X.S20221228
Citation: Yue XU, Chan WANG, Shucheng LIN, Huijie ZHANG, Yi TAN, Shuwei ZHANG, Xiaofeng ZENG, Zhen LI. Advances in the Mechanism of Hepatotoxic Effects Induced by α-amanitin[J]. Journal of Kunming Medical University, 2022, 43(12): 153-158. doi: 10.12259/j.issn.2095-610X.S20221228

α-鹅膏毒肽诱导肝细胞毒性作用机制的研究进展

doi: 10.12259/j.issn.2095-610X.S20221228
基金项目: 国家自然科学基金资助项目(81960340)
详细信息
    作者简介:

    许悦(1995~),女,贵州盘州人,医学硕士,主要从事法医毒理学研究工作

    通讯作者:

    曾晓锋,E-mail:zxf2004033@163.com

    李桢,E-mail:lizhenlaura@126.com

  • 中图分类号: R89

Advances in the Mechanism of Hepatotoxic Effects Induced by α-amanitin

  • 摘要: 鹅膏菌是一类可引起急性中毒的蘑菇种属,90%以上野生菌中毒死亡事件均由鹅膏毒肽引发,α-鹅膏毒肽(α-amanitin、α-AMA)是其中毒性最强的成分,肝脏是其毒性靶器官。RNA聚合酶Ⅱ(RNA pol Ⅱ)转录抑制是α-鹅膏毒肽导致肝细胞损伤的公认机制,但其他可能的毒理学机制尚待阐明。主要从α-鹅膏毒肽诱导肝细胞凋亡、自噬、炎症、氧化应激等毒性机制,中毒后临床治疗等方面进行综述,旨在为鹅膏毒肽中毒研究以及防治提供新的思路。
  • [1] 魏佳会,吴剑峰,陈佳,等. 12种剧毒鹅膏菌的肽类毒素成分鉴定及其相对含量差异比较研究[J]. 分析化学,2017,45(6):817-823. doi: 10.11895/j.issn.0253-3820.170001
    [2] 李娟娟,万蓉,万青青,等. 2015年云南省野生菌中毒分析[J]. 职业与健康,2016,32(16):2207-2209,2213. doi: 10.13329/j.cnki.zyyjk.2016.0696
    [3] 王晶,史振霞,乔洁,等. 毒鹅膏菌和鹅膏肽类毒素研究进展[J]. 廊坊师范学院学报(自然科学版),2018,18(1):46-53. doi: 10.3969/j.issn.1674-3229.2018.01.011
    [4] Rodrigues D F,Pires das Neves R,Carvalho ATP,et al. In vitro mechanistic studies on α-amanitin and its putative antidotes[J]. Arch Toxicol,2020,94(6):2061-2078. doi: 10.1007/s00204-020-02718-1
    [5] Santi L,Maggioli C,Mastroroberto M,et al. Acute liver failure caused by Amanita phalloides poisoning[J]. Int J Hepatol,2012,2012:487-480. doi: 10.1155/2012/487480
    [6] Matinkhoo K,Pryyma A,Todorovic M,et al. Synthesis of the death-cap mushroom toxin α-Amanitin[J]. J Am Chem Soc,2018,140(21):6513-6517. doi: 10.1021/jacs.7b12698
    [7] Liu X,Farnung L,Wigge C,et al. Cryo-EM structure of a mammalian RNA polymerase II elongation complex inhibited by α-amanitin[J]. J Biol Chem,2018,293(19):7189-7194. doi: 10.1074/jbc.RA118.002545
    [8] 赵春艳,王婷婷,邰丽梅,等. 鹅膏菌肽类毒素的研究进展[J]. 中国食用菌,2014,33(4):9-11,13. doi: 10.13629/j.cnki.53-1054.2014.04.003
    [9] Diaz J H. Amatoxin-containing mushroom poisonings:Species,toxidromes,treatments,and outcomes[J]. Wilderness Environ Med,2018,29(1):111-118. doi: 10.1016/j.wem.2017.10.002
    [10] 余成敏,李海蛟. 中国含鹅膏毒肽蘑菇中毒临床诊断治疗专家共识[J]. 中华急诊医学杂志,2020,29(2):171-179. doi: 10.3760/cma.j.issn.1671-0282.2020.02.008
    [11] 杨艳,邵瑞飞,陈国兵. 蘑菇中毒机制研究进展[J]. 临床急诊杂志,2020,21(8):675-678. doi: 10.13201/j.issn.1009-5918.2020.08.016
    [12] Sun J,Li H J,Zhang H S,et al. Investigating and analyzing three cohorts of mushroom poisoning caused by Amanita exitialis in Yunnan,China[J]. Hum Exp Toxicol,2018,37(7):665-678. doi: 10.1177/0960327117721960
    [13] Marciniak B, Łopaczyńska D, Ferenc T. Evaluation of the genotoxicity of alpha-amanitin in mice bone marrow cells[J]. Toxicon, 2017 , 137(期?): 1-6. DOI: 10.1016/j.toxicon.2017.07.005. doi: 10.1016/j.toxicon.2017.07.005

    Marciniak B,Łopaczyńska D,Ferenc T. Evaluation of the genotoxicity of alpha-amanitin in mice bone marrow cells[J]. Toxicon,2017,137:1-6. doi: 10.1016/j.toxicon.2017.07.005
    [14] Ivleva E A,Bogomolov D V,Putintsev V A,et al. Osobennosti morfologicheskikh proiavleniĭ porazheniia pecheni pri otravlenii blednoĭ pogankoĭ [The peculiar features of the morphological manifestations of the damage to the liver associated with the death cap mushroom poisoning][J]. Sud Med Ekspert,2017,60(3):23-26. doi: 10.17116/sudmed201760323-26
    [15] 孙晓琳,赵娣,李军袖,等. 有机阴离子转运多肽OATP1B1、OATP1B3的基因多态性及其介导的药物相互作用研究进展[J]. 中国临床药理学与治疗学,2015,20(11):1296-1301.
    [16] Letschert K,Faulstich H,Keller D,et al. Molecular characterization and inhibition of amanitin uptake into human hepatocytes[J]. Toxicol Sci,2006,91(1):140-149. doi: 10.1093/toxsci/kfj141
    [17] Siegert M J,Knittel C H,Süssmuth R D. A Convergent Total Synthesis of the Death Cap Toxin α-Amanitin[J]. Angew Chem Int Ed Engl,2020,59(14):5500-5504. doi: 10.1002/anie.201914620
    [18] Graeme K A. Mycetism:A review of the recent literature[J]. J Med Toxicol,2014,10(2):173-189. doi: 10.1007/s13181-013-0355-2
    [19] Bushnell D A,Cramer P,Kornberg R D. Structural basis of transcription:alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution[J]. Proc Natl Acad Sci U S A,2002,99(3):1218-1222. doi: 10.1073/pnas.251664698
    [20] Chen X, Shao B, Yu C, et al. The cyclopeptide -amatoxin induced hepatic injury via the mitochondrial apoptotic pathway associated with oxidative stress[J]. Peptides, 2020 , 129(期?): 170314. DOI: 10.1016/j.peptides.2020.170314. doi: 10.1016/j.peptides.2020.170314

    Chen X,Shao B,Yu C,et al. The cyclopeptide -amatoxin induced hepatic injury via the mitochondrial apoptotic pathway associated with oxidative stress[J]. Peptides,2020,129:170314. doi: 10.1016/j.peptides.2020.170314
    [21] Arima Y,Nitta M,Kuninaka S,et al. Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria[J]. J Biol Chem,2005,280(19):19166-19176. doi: 10.1074/jbc.M410691200
    [22] 徐赛群,朱小寒,刘斌,等. α-鹅膏蕈碱诱导小鼠肝细胞凋亡的实验研究[J]. 中华急诊医学杂志,2005,14(2):115-118. doi: 10.3760/j.issn:1671-0282.2005.02.009
    [23] Magdalan J,Ostrowska A,Piotrowska A,et al. Alpha-amanitin induced apoptosis in primary cultured dog hepatocytes[J]. Folia Histochem Cytobiol,2010,48(1):58-62. doi: 10.2478/v10042-010-0010-6
    [24] Bonnet M S,Basson P W. The toxicology of Amanita phalloides[J]. Homeopathy,2002,91(4):249-254. doi: 10.1054/homp.2002.0056
    [25] Nikoletopoulou V,Markaki M,Palikaras K,et al. Crosstalk between apoptosis,necrosis and autophagy[J]. Biochim Biophys Acta,2013,1833(12):3448-3459. doi: 10.1016/j.bbamcr.2013.06.001
    [26] Chen X, Shao B, Yu C, et al. Energy disorders caused by mitochondrial dysfunction contribute to α-amatoxin-induced liver function damage and liver failure[J]. Toxicol Lett, 2021 , 336(期?): 68-79. DOI: 10.1016/j.toxlet.2020.10.003. doi: 10.1016/j.toxlet.2020.10.003

    Chen X,Shao B,Yu C,et al. Energy disorders caused by mitochondrial dysfunction contribute to α-amatoxin-induced liver function damage and liver failure[J]. Toxicol Lett,2021,336:68-79. doi: 10.1016/j.toxlet.2020.10.003
    [27] Gu X,Zhang L,Sun W,et al. Autophagy promotes α-amanitin-Induced apoptosis of aepa1-6 liver cells[J]. Chem Res Toxicol,2022,35(3):392-401. doi: 10.1021/acs.chemrestox.1c00297
    [28] 王改平,李晓芳,陈莎莎,等. 肝脏炎症反应与肝再生关系的研究进展[J]. 中国免疫学杂志,2015,31(8):1115-1119. doi: 10.3969/j.issn.1000-484X.2015.08.027
    [29] 曹玫,颜亮,聂远洋,等. 环肽α-amanitin在小鼠体内的毒性作用研究[J]. 四川大学学报(医学版),2009,40(5):901-904. doi: 10.3969/j.issn.1672-173X.2009.05.032
    [30] Zheleva A,Tolekova A,Zhelev M,et al. Free radical reactions might contribute to severe alpha amanitin hepatotoxicity-a hypothesis[J]. Med Hypotheses,2007,69(2):361-367. doi: 10.1016/j.mehy.2006.10.066
    [31] Dündar Z D,Ergin M,Kilinç İ,et al. The role of oxidative stress in α-amanitin-induced hepatotoxicityin an experimental mouse model[J]. Turk J Med Sci,2017,47(1):318-325. doi: 10.3906/sag-1503-163
    [32] Ergin M,Dundar Z D,Kilinc I,et al. Alpha-amanitin poisoning,nephrotoxicity and oxidative stress:An experimental mouse model[J]. Iran Red Crescent Med J,2015,17(8):e28068. doi: 10.5812/ircmj.28068
    [33] Magdalan J,Piotrowska A,Gomułkiewicz A,et al. Influence of commonly used clinical antidotes on antioxidant systems in human hepatocyte culture intoxicated with alpha-amanitin[J]. Hum Exp Toxicol,2011,30(1):38-43. doi: 10.1177/0960327110368418
    [34] Tse H N, Tseng C Z. Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis, 2014 , 9(期?): 825-836. DOI: 10.2147/COPD.S51057. doi: 10.2147/COPD.S51057

    Tse H N,Tseng C Z. Update on the pathological processes,molecular biology,and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2014,9:825-836. doi: 10.2147/COPD.S51057
    [35] Poucheret P,Fons F,Doré J C,et al. Amatoxin poisoning treatment decision-making:Pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis[J]. Toxicon,2010,55(7):1338-1345. doi: 10.1016/j.toxicon.2010.02.005
    [36] Garcia J,Costa V M,Carvalho A T,et al. A breakthrough on Amanita phalloides poisoning:An effective antidotal effect by polymyxin B[J]. Arch Toxicol,2015,89(12):2305-2323. doi: 10.1007/s00204-015-1582-x
    [37] 马星海. 水飞蓟化学成分和药理作用研究进展[J]. 亚太传统医药,2015,11(19):62-65.
    [38] 陈汝静,吴云杰,胡凯莉. 水飞蓟宾药理作用研究进展[J]. 上海中医药杂志,2021,55(2):90-96.
    [39] Mengs U,Pohl R T,Mitchell T. Legalon® SIL:The antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning[J]. Curr Pharm Biotechnol,2012,13(10):1964-1970. doi: 10.2174/138920112802273353
    [40] 钱梦茹. 多粘菌素B的作用机制研究新进展[J]. 甘肃医药,2019,38(5):397-399,421. doi: 10.15975/j.cnki.gsyy.2019.05.005
    [41] Garcia J,Costa V M,Bovolini A,et al. An effective antidotal combination of polymyxin B and methylprednisolone for α-amanitin intoxication[J]. Arch Toxicol,2019,93(5):1449-1463. doi: 10.1007/s00204-019-02426-5
    [42] Sahin A,Arici M A,Yilmaz Y,et al. A comparison of the effectiveness of silibinin and resveratrol in preventing alpha-amanitin-induced hepatotoxicity[J]. Basic Clin Pharmacol Toxicol,2018,122(6):633-642. doi: 10.1111/bcpt.12954
    [43] Arici M A,Sahin A,Cavdar Z,et al. Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice[J]. Hum Exp Toxicol,2020,39(3):328-337. doi: 10.1177/0960327119888271
    [44] Trabulus S,Altiparmak M R. Clinical features and outcome of patients with amatoxin-containing mushroom poisoning[J]. Clin Toxicol (Phila),2011,49(4):303-310. doi: 10.3109/15563650.2011.565772
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出版历程
  • 收稿日期:  2022-04-19
  • 网络出版日期:  2022-12-06
  • 刊出日期:  2022-12-25

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