鹅膏菌属蘑菇中毒导致的死亡占我国食物中毒死亡的90%，α-鹅膏毒肽是其主要毒素之一，诱导肝脏损伤。对于α-鹅膏毒肽中毒还未有完全有效的治疗手段，所以寻找新的治疗靶点是当务之急。研究发现，一种黑腹果蝇能够耐受α-鹅膏毒肽。全基因组关联研究表明，丝氨酸/苏氨酸蛋白磷酸酶2A（PP2A）是耐受过程中的关键蛋白，且其作用与细胞自噬密切相关。已有大量研究表明，PP2A一方面能调节Akt/mTOR路径，另一方面对自噬相关蛋白如Beclin 1等进行去磷酸化修饰，进而调控自噬。据此，我们提出假设“PP2A调控的细胞自噬在α-鹅膏毒肽诱导的肝损伤中起到了非常重要的作用”。所以，本项目拟利用基因干预和药理学方法，通过体外和体内试验，探究PP2A-Akt/Beclin 1信号路径在细胞自噬中的作用机制，阐明细胞自噬在α-鹅膏毒肽诱导的小鼠肝损伤中的作用，为α-鹅膏毒肽的毒理机制研究及治疗靶点的发现提供依据。

The death rate caused by accidental digestion of amanita accounts for 90% of the death from food poisoning in China. The major toxin of amanita is α-amanitin which could induce liver damage. However, there is no completely valid treatment for α-amanitin poisoning, therefore it is urgent to find new therapeutic targets. It has been reported that a kind of Drosophila melanogaster is resistant to α-amanitin. The genome-wide association studies revealed that Ser/Thr Phosphatase Protein Phosphatase 2A (PP2A) is a key protein during the resistant process, which is associated with autophagy. A large number of documents have demonstrated that PP2A could regulate autophagy via affecting Akt/mTOR pathway and dephosphorylating autophagy-related proteins such as Beclin 1. Hereby, the hypothesis "PP2A-mediated autophagy plays a critical role in α-amanitin-induced liver damage" is proposed. Therefore, the research was conducted to investigate the effect of mechanism of PP2A-Akt/Beclin 1 signaling pathway in autophagy in vitro and in vivo, and to elucidate the effect of autophagy in α-amanitin-induced mouse liver damage. This study eventually provides a fundament for the research of the toxicological mechanism of α-amanitin and the uncovering of therapeutic targets.