黄曲霉毒素B_(1)致病机制及防治研究进展

Research Progress on Pathogenic Mechanism and Control of Aflatoxin B_(1)

黄曲霉毒素(aflatoxins,AFs)是一类来自于霉菌中的剧毒物质,其中以黄曲霉毒素B_(1)(aflatoxin B_(1),AFB_(1))的毒性最强、危害性最大。AFB_(1)是一种具有强致癌性及剧烈毒性的双呋喃环类毒素,广泛分布于霉变的玉米、花生、大米和大豆等粮油作物中,由AFB_(1)引发的人与动物中毒事件给当前食品安全和畜禽养殖等行业的发展造成了严重危害。AFB_(1)已被证明能够引起机体氧化应激、细胞凋亡、细胞焦亡、基因突变及免疫系统损伤。作者阐述了AFB_(1)抑制机体免疫系统、破坏机体免疫耐受性的免疫毒性作用;介绍了AFB_(1)促进活性氧生成、激活Nrf2-ARE通路、诱导机体氧化应激和炎症反应进而造成器官损伤的器官毒性作用;分析了AFB_(1)利用细胞死亡相关受体调控外源性细胞凋亡作用,以及通过一系列细胞凋亡相关蛋白诱导内源性细胞凋亡作用,还可利用肝细胞经典焦亡途径引发炎症反应,继而引发非正常死亡的细胞毒性作用;回顾了近年来关于AFB_(1)基因毒性与其去毒措施的作用机制及其研究进展。本综述有望为针对AFB_(1)致病机制的深入研究及相关防治药物的研发提供参考,并为发霉粮油作物的去毒措施的选择提供有效依据。

Aflatoxins(AFs)are a kind of poisonous substances from mold,among which aflatoxins B_(1)(AFB_(1))is the most toxic and harmful.AFB_(1)is a bifuranocyclic toxin with strong carcinogenicity and intense toxicity,which is widely distributed in moldy corn,peanut,rice and soybean and other food and oil crops,human and animal poisoning caused by AFB_(1)has resulted in serious harm to food safety,livestock breeding and other industries.AFB_(1)has been shown to cause oxidative stress,apoptosis,cytotoxicity,gene mutation and immune system damage.The immunotoxic effects of AFB_(1)on inhibiting immune system and destroying immune tolerance were discussed.AFB_(1)promotes the production of reactive oxygen species and activates the Nrf2-ARE pathway to induce oxidative stress and inflammatory response,thus causing organ damage.AFB_(1)regulates exogenous apoptosis through cell death-related receptors and induces endogenous apoptosis through a series of apoptosis-related proteins.AFB_(1)can also trigger inflammatory response through the classical pyroapoptotic pathway of liver cells,which can lead to abnormal cell death.The mechanism and research progress of AFB_(1)genotoxicity and its detoxification measures were reviewed.This review is expected to provide a reference for in-depth research on the pathogenic mechanism of AFB_(1)and the development of related control drugs,and afford an effective basis for the selection of detoxification measures for moldy grain and oil crops.