单纯性脂肪肝到脂肪性肝炎（NASH）为非酒精性脂肪性肝病发展过程中的关键步骤，IL-1β在肝脏脂代谢紊乱过程中发挥重要作用。体内IL-1β的成熟及分泌与NLRP3炎症小体的激活密切相关,但NLRP3炎症小体激活的具体机制尚不清楚。NLRP3炎症小体的激动剂均不能直接激活该炎症小体，最近研究发现硫氧还蛋白相互作用蛋白（TXNIP）可能为连接激动剂与该炎症小体的重要桥梁。我们前期研究表明Kupffer细胞（KCs）是多种炎症介质分泌的主要场所，因此推测KCs亦是各种应激刺激导致NLRP3炎症小体激活并分泌IL-1β的主要部位。本研究以KCs为主要靶细胞，通过激光共聚焦等技术研究高游离脂肪酸状态下KCs中TXNIP与NLRP3的结合情况；采用敲除TXNIP与NLRP3基因的方法，探讨TXNIP在介导KCs中NLRP3炎症小体激活的确切机制，为进一步研究NASH的发生机制做一些探索性工作。

The change from simple steatosis to nonalcoholic steatohepatitis is a key step in the development of nonalcoholic fatty liver disease, and IL-1β played an important role in the process of hepatic lipid metabolism disorder. The maturation and secretion of IL-1β is closely related to the activation of NLRP3 inflammasome. However, the mechanism of the activation of NLRP3 inflammasome is not clear yet. The agonists of NLRP3 inflammasome could not activate the NLRP3 inflammasome directly. A recent research found that thioredoxin-interacting protein (TXNIP) might be a significant medium which bridges the agonists and NLRP3 inflammasome. In our preliminary study, we found that Kupffer cell is the primary position of the secretion of various pro-inflammatory cytokines, consequently, we reckon that Kupffer cell is the primary position of the activation of NLRP3 inflammasome and the secretion of IL-1β in the inflamatory condition. We take the Kupffer cell as the major target cell, and discuss the mechanism of the activation of NLRP3 inflammasome by TXNIP in Kupffer cell, to further study the pathogenesis of NASH.