中文摘要：黄曲霉和寄生曲霉产生的真菌代谢物造成人畜健康危害。特别是黄曲霉毒素B1（AFB1）是研究最多且全球熟知的致癌物，产生影响多种生物的肝毒性、遗传毒性和免疫毒性。已知AFB1通过引起肝细胞凋亡和干扰细胞酶活性引发肝功能障碍。在肝脏中，AFB1通过死亡受体途径高表达这一外在机制引起细胞凋亡，而其详细机制尚不清楚。为此本研究用AFB1饲喂小鸡3周，探索AFB1诱导的肝细胞凋亡中由死亡受体及相关基因引发的凋亡机制。本研究结果包括组织病理学、超微结构、流式细胞学和死亡受体通路的基因表达谱，新颖而全面，将有助于更好地理解由AFB1引起的死亡受体路径的机制，并且可能最终降低AFB１的产毒潜力。
外文摘要：The fungal metabolites produced by Aspergillus flavus and Aspergillus parasiticus cause detrimental health effects on humans and animals. Particularly aflatoxin B1 (AFB1) is the most studied and a well-known global carcinogen, producing hepatotoxic, genotoxic and immunotoxic effects in multiple species. AFB1 is shown to provoke liver dysfunctioning by causing hepatocytes apoptosis and disturbing cellular enzymatic activities. In liver, AFB1 causes apoptosis via extrinsic mechanism because of high expression of death receptor pathway. The detailed mechanism of AFB1 induced hepatocytes apoptosis, via death receptor pathway still remains elusive. So the present study was conducted to explore apoptotic mechanism initiated by death receptors and associated genes in aflatoxin B1 induced liver apoptosis in chickens fed with AFB1 for 3 weeks. Results from the present study displayed histopathological and ultrastructural changes in liver such as hydropic degeneration, fatty vacuolar degeneration and proliferation of bile duct in hepatocytes in AFB1 group, along with imbalance between reactive oxygen species (ROS) and antioxidant defense system upon AFB1 ingestion. Moreover, AFB1 intoxicated chickens showed upregulation of death receptors FAS, TNFR1 and associated genes and downregulation of inhibitory apoptotic proteins XIAP and BCL-2. The results obtained from this novel and comprehensive study including histopathological, ultrastructural, flow cytometrical and death receptor pathway gene expression profiles, will facilitate better understanding of mechanisms and involvement of death receptor pathway in hepatocytes apoptosis induced by AFB1 and ultimately may be helpful in bringing down the toxigenic potential of AFB1.
外文关键词：aflatoxin B1；apoptosis；carcinogenicity；oxidative stress；hepatotoxicity
作者：Mughal, MJ；Peng, X；Zhou, Y；Fang, J
作者单位：Sichuan Agr Univ
期刊名称：ONCOTARGET
期刊影响因子：5.008
出版年份：2017
出版刊次：5
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