自噬在不同组织的放射应答中起不同作用：既可能是机体自我保护机制，也可能是加重放射损伤的因素。如何利用自噬的"两面性"，舍弊取利，是自噬研究的焦点。我们前期研究表明：涎腺放射后自噬基因及蛋白上调，自噬水平上调，IGF-1结合蛋白IGFBP3表达降低，腺泡分泌功能减弱。由此推断：自噬在放射性涎腺损伤的发病中发挥一定作用。然而，自噬是否为放射损伤发生的主要因素，其调控机制如何，这些关键问题尚待探讨。本课题拟在前期研究基础上，进一步探讨放射后自噬水平改变及对涎腺细胞性状、分泌功能的影响；阐明IGF-1/PI3K/PKB通路调控放射后涎腺细胞自噬的分子机制；通过课题组首创的分割放射后涎腺功能损伤动物模型，体内研究IGF-1/PI3K/PKB信号通路介导自噬预防放射性涎腺损伤的作用；最后，临床验证放射后涎腺自噬水平与功能损伤相关的结论。课题将揭示自噬在放射性涎腺功能损伤中所扮演的角色及其调控分子机制。

Autophagy, the process by which cells recycle cytoplasm and dispose of excess or defective organelles, plays different roles in radiation induced tissue and organs damage. It may protect the body, or in contrast, aggravate the damage. Therefore, autophagy, as a double-edged sword with therapeutic potential, becomes the focus of research in recent years. Our previous study showed that there was an up-regulation of autophagy-related genes and proteins in the acute stage of radiation induced salivary gland hypofunction, which indicated an increase of autophagy level. Also, we observed that the expression of IGF-1 binding protein-3 (IGFBP3) was significantly reduced. The functional study verified that the secretion function of acini was decreased. Altogether these preliminary results suggest that autophagy is involved in the pathophysiology of radiation induced salivary gland hypofunction. However, the exact role of autophagy in the etiology of radiation induced salivary gland hypofunction and its regulation mechanism is unknown. Therefore, we hypothesize that increased autophagy level plays a critical role in the etiology of radiation induced salivary gland hypofunction and IGF-1/PI3K/PKB pathway regulates this process. To test this hypothesis, we will firstly evaluate the alteration of autophagy levels after irradiation and its relationship with IGF-1/PI3K/PKB pathway and acini secretion function. Next the autophagy levels will be up- or down-regulated by IGF-1/PI3K/PKB pathway, and the secretion function will be quantitatively assessed. Then, we tend to prevent radiation induced salivary gland hypofunction by regulation of autophagy in vivo using the animal mode of rabbit salivary gland injury after fractionated radiotherapy, which was firstly published by our research group in 2012. Finally, we will assess the relationship between the autophagy levels and salivary gland function in patients receiving radiotherapy for head and neck cancers. The present study will test our hypothesis and illustrate the role of autophagy in radiation induced salivary gland hypofunction and its molecular regulation mechanism during this process.