赭曲霉毒素A(OTA)是广泛存在于饲料中的一种具有很强肾毒性和免疫毒性的霉菌毒素。硒化黄芪多糖是一种有机硒多糖，具有比硒、黄芪多糖或硒加黄芪多糖更好的抗氧化功效。我们前期研究表明硒可通过抗氧化作用减弱OTA对猪肾细胞的毒性。但迄今有关OTA毒性的自噬机制，硒化黄芪多糖减弱OTA毒性的作用与机制未见研究。本项目拟以猪肾细胞和猪肺泡巨噬细胞为模型，应用透射电镜、流式细胞术、蛋白免疫印迹等技术研究硒化黄芪多糖减弱OTA对猪肾毒性和免疫毒性的作用；进一步应用GFP-LC3转染、激光共聚焦、RNA干扰等技术，通过应用自噬调控剂（如自噬激活剂雷帕霉素，自噬抑制剂氯喹、3-MA）和干扰自噬相关基因（Atg5、Atg7、Beclin-1等）研究OTA对猪肾毒性和免疫毒性的自噬机制，硒化黄芪多糖减弱OTA肾毒性和免疫毒性的自噬机制。本项目可为猪OTA中毒的防控及硒化黄芪多糖在畜牧生产上的应用提供科学依据。

Ochratoxin A is a world-wide potent nephrotoxin and immunotoxin that naturally occurs in food and feeds. Selenylation modification of astragalus polysaccharide is an organic selenylation modification of polysaccharide, and has the better antioxidant function than selenium or/and astragalus polysaccharide. Our previous studies indicated that selenium alleviated ochratoxin A-induced nephrotoxicity by improving antioxidant function. However, the autophagy mechanism of ochratoxin A -induced toxicity and the effects of selenylation modification of astragalus polysaccharide on ochratoxin A -induced cytotoxicity and their mechanism have not been reported until now. The contents of the project are as follows by using the porcine kidney 15 cells and porcine alveolar macrophage cells as the models: investigation autophagy mechanism of ochratoxin-induced toxicity; the effects of selenylation modification of astragalus polysaccharide on ochratoxin A-induced nephrotoxicity and immunotoxicity; the autophagy mechanism of the protective effects of selenylation modification of astragalus polysaccharide on ochratoxin A-induced nephrotoxicity and immunotoxicity by the autophagy control agent (such as autophagy activator rapamycin, autophagy inhibitor chloroquine, 3 - MA) and interferencing autophagy-related gene (Atg5, Atg7, Beclin-1 and so on). Some advanced technologies such as transmission electron microscopy, flow cytometry, western blotting, GFP-LC3 transfection, confocal laser, and RNA interference will be used in the project. The project provides the prevention and control of ochratoxin A-poisoning in pig, and a scientific basis for the selenylation modification of astragalus polysaccharide use in livestock production.