mTOR信号通路在T-2毒素神经毒性中的作用研究

T-2 毒素是A类单端孢霉烯族真菌毒素中毒性最强，危害极为严重的一种真菌毒素。T-2毒素严重污染粮食作物、饲料原料及其加工产品，被污染饲料严重威胁畜禽健康，对畜禽养殖业的影响极大。此外，T-2毒素及其在动物体内的代谢产物将在动物可食性组织器官残留，通过食物链传递到人类，严重威胁人类健康。本实验室前期研究结果显示T-2毒素诱导神经毒性时，Nrf2被抑制，mTOR被激活，p53蛋白表达量上调，表明mTOR信号通路可能在T-2毒素诱导的神经毒性中扮演着重要角色。因此，本项目建立T-2毒素正常小鼠、基因敲除鼠神经毒性模型并使用小鼠大脑皮层原代神经元细胞、Neuro-2a细胞为体外模型，研究mTOR信号通路在T-2毒素神经毒性过程的作用机理，研究结果将为深入阐明T-2毒素的神经毒性作用机制，科学提出T-2毒素减毒措施，保障畜禽生产安全和人类健康提供科学依据。

T-2 toxin is the most toxic and endangered mycotoxins of class A trichothecene mycotoxins. T-2 toxin seriously pollutes food crops, feed raw materials and their processed products. The contaminated feed poses a serious threat to the health of livestock and has a great impact on livestock and poultry breeding. In addition, T-2 toxin and their metabolites will remain in animal edible tissues and organs. It will be transmitted to humans through the food chain, posing a serious threat to human health. A large number of studies have been carried out in our laboratory. The results showed that Nrf2 was inhibited, mTOR was activated and p53 protein expression was increased in T-2 toxin-induced neurotoxicity, which indicated that mTOR signal pathway may be played an important role in T-2 toxin-induced neurotoxicity. Therefore, the neurotoxicity model of T-2 toxin in mice and gene knockout mice was established, and the primary neuron cells and Neuro-2a cells of mouse cerebral cortex were used as in vitro models to study the mechanism of mTOR signaling pathway in the neurotoxicity of T-2 toxin. The results will further elucidate the neurotoxic mechanism of T-2 toxin, and provide scientific data for detoxification measures, livestock production safety and human health.