我们前期的动物研究发现，高脂饮食可诱导糖尿病前期周围神经病变的发生，并且周围神经硫氧还蛋白（TRX）相互作用蛋白（TXNIP）表达增加。近年来越来越多的研究发现TXNIP表达增加可促进细胞凋亡并激活NLRP3炎症体导致炎症反应，有学者提出TXNIP的线粒体穿梭可能是氧化应激与炎症体激活的重要联系。据此我们提出TXNIP的线粒体穿梭诱发下游凋亡信号促使炎症反应可能导致了神经细胞的凋亡和神经的炎性损伤，这可能是高脂饮食导致糖尿病前期周围神经病变的重要机制。本研究分别进行动物和细胞实验，探讨在高脂条件下，使用钙离子拮抗剂或RNA干扰下调TXNIP表达，检测细胞凋亡指标和炎症相关蛋白的表达变化，应用激光共聚焦和免疫共沉淀分别观察TXNIP在亚细胞组分的分布变化以及相关蛋白的结合情况。TXNIP的表达或穿梭途径可能成为新的靶点，为干预和逆转高脂饮食所诱导的糖尿病前期周围神经病变提供新的思路。

Our pilot animal study confirmed that high-fat-diet can induce pre-diabetic peripheral neuropathy, and the expression of thioredoxin (TRX) interacting protein (TXNIP) increased in peripheral nerve. In recent years, a growing number of studies have found that increased expression of TXNIP may lead to cell apoptosis and NLRP3 inflammasome activation, and some scholars suggest that mitochondrial shuttling of TXNIP may be an important link between oxidative stress and inflammasome activation. Accordingly, we propose that mitochondrial shuttling of TXNIP induce downstream apoptotic signaling and promote inflammation, which lead to neuronal cell apoptosis and nerve inflammatory injury. This may be an important mechanism of high-fat-diet induced pre-diabetic peripheral neuropathy. In the present study, we designed animal and cell experiments respectively. Under high-fat conditons, the expression of TXNIP was down-regulated by calcium antagonist or siRNA, and we would detect apoptotic indicators and the expression of inflammation related proteins. We would also observe the distribution changes of TXNIP and interactions of associated proteins in subcellular compartments by laser scanning confocal microscope and co-immunoprecipitation respectively. We speculate that TXNIP expression and the shuttling pathway may become new targets for preventing and reversing high-fat-diet induced pre-diabetic peripheral neuropathy.