Yan Jiahui, Chen Lin, Zhang Li, Zhang Zhaohuan, Zhao Yong, Wang Yuan, Ou Jie
College of Food Sciences and Technology, Shanghai Ocean University, Shanghai, China.
Engineering Research Center of Modern Preparation Technology of TCM, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Microbiol. 2022 Jun 16;13:911757. doi: 10.3389/fmicb.2022.911757. eCollection 2022.
Aflatoxin B (AFB) has mutagenesis, carcinogenesis and teratogenesis effects and mainly found in food crops and their processed foods. AFB exposure can cause acute or chronic liver poisoning, but there were few studies on the persistent effects of acute AFB exposure on the liver. In this study, rat liver injury models were established 2 and 7 days after single exposure to high and low doses of AFB. The persistent effects of AFB single acute exposure (ASAE) on rat liver were analyzed from the phenotypic and genetic levels. The results showed that compared with the control group, liver function indexes, MDA content in liver and the number of apoptotic hepatocytes in model groups increased to the highest on the 2nd day after ASAE ( < 0.001). However, the changes of liver coefficient were most significant on the 7th day after ASAE ( < 0.01). The results of liver pathology showed that the liver injury was not alleviated and the activities of antioxidant enzymes GSH-Px and SOD were the lowest on the 7th day ( < 0.001). RNA-Seq results indicated that there were 236, 33, 679, and 78 significantly differentially expressed genes (DEGs) in the model groups (LA-2d, LA-7d, HA-2d, HA-7d) compared with the control group. Among them, the gene related to the proliferation, differentiation and metastasis of liver cancer cells, the and gene related to the inflammatory response were significantly DEGs in the four model groups, and the differential expression of the immune system-related Bcl6 gene increased with the prolonged observation time after ASAE. In conclusion, ASAE can cause persistent liver damage in rats. The persistently affected genes , , , and 6 possess the potential to be therapeutic targets for liver disease induced by AFB.
黄曲霉毒素B（AFB）具有致突变、致癌和致畸作用，主要存在于粮食作物及其加工食品中。接触AFB可导致急性或慢性肝中毒，但关于急性AFB暴露对肝脏的持续影响的研究较少。在本研究中，在单次暴露于高剂量和低剂量AFB后的第2天和第7天建立大鼠肝损伤模型。从表型和基因水平分析AFB单次急性暴露（ASAE）对大鼠肝脏的持续影响。结果显示，与对照组相比，模型组肝功能指标、肝脏丙二醛（MDA）含量及凋亡肝细胞数量在ASAE后第2天升至最高（<0.001）。然而，肝脏系数变化在ASAE后第7天最为显著（<0.01）。肝脏病理学结果显示，肝损伤未缓解，抗氧化酶谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）活性在第7天最低（<0.001）。RNA测序结果表明，与对照组相比，模型组（LA-2d、LA-7d、HA-2d、HA-7d）中有236、33、679和78个显著差异表达基因（DEG）。其中，与肝癌细胞增殖、分化和转移相关的基因，以及与炎症反应相关的基因和基因在四个模型组中均为显著DEG，且免疫系统相关Bcl6基因的差异表达随ASAE后观察时间延长而增加。总之，ASAE可导致大鼠肝脏持续性损伤。持续受影响的基因、、和6具有成为AFB所致肝病治疗靶点的潜力。
