葡萄糖调节蛋白78（GRP78），在内质网应激中发挥了重要的调节作用。氟可以诱导成釉细胞出现内质网应激反应(ERs)，同时伴有自噬反应的发生。这两种现象的出现是否为因果关系，其调节机制如何？自噬反应的出现是减轻还是加重了氟的毒性作用是本研究关心和拟解决的课题。根据前期研究基础，我们提出假设：当氟化物作用于成釉细胞时，内质网应激反应被激活，GRP78通过GRP78-IRE1-TRAF2-JNK通路调控自噬反应，以应对氟对成釉细胞的毒性作用。本研究通过动物实验和离体细胞培养试验，采用染氟成釉细胞转染双标LC3腺病毒、通过建立干扰和过表达GRP78稳转细胞株，采用沉默基因表达和抑制酶活性等手段开展以下研究：1.成釉细胞内的自噬反应与氟中毒的关系及其作用；2. 内质网分子伴侣与自噬的关系及可能的调节机制。该课题的研究有利于增加对氟牙症发病的分子生物学机制的认识，为预防氟牙症的发提供新的思路和新途径

Glucose regulated protein 78 (GPR78) plays an important role in endoplasmic reticulum stress. Fluoride can induce the endoplasmic reticulum stress response in the ameloblast, and reduce the toxicity of fluoride by autophagy, maintain the stability of the cells. The excessive Glucose regulated protein 78 (GRP78) plays an important role in endoplasmic reticulum stress. Fluoride can induce the endoplasmic reticulum stress response in the ameloblast and autophagy reactions at the same time. Whether the occurrence of these two phenomena is causality, how is its regulating mechanism? This study concerns and intends to solve the problem that the occurrence of autophagy is to reduce or aggravate the toxicity of fluoride. According to our previous studies, we supposed that fluoride induced endoplasmic reticulum stress in ameloblast, and through the GRP78- IRE1-TRAF2-JNK pathway regulated ameloblast autophagy, which reduced cytotoxicity of ameloblast. This research attempts to verify the hypothesis through animal experiments and cell culture experiments. We adopt ameloblast transfection of mRFP-GFP-LC3, overexpression and interference of GRP78 transfect in ameloblast, and siRNA and inhibits methods to study following problems:1. the relationship between autophagy and fluorosis in ameloblast and its roles. 2. the relationship between endoplasmic reticulum molecular chaperone and autophagy and these possible regulatory mechanisms This subject is helpful to increase the understanding of the molecular biological mechanism of dental fluorosis, and provide a theoretical basis for the prevention and treatment of dental fluorosis.