益气温阳方介导HMGB1/mTOR通路调控紧密连接蛋白治疗变应性鼻炎的机制研究

变应性鼻炎（AR）是与鼻粘膜屏障功能受损密切相关的耳鼻喉科常见慢性病，远期疗效并不理想，易反复发作。紧密连接（TJ）蛋白是维护粘膜屏障的重要结构。最新研究表明TJ蛋白受损导致鼻粘膜屏障功能被破坏是AR发病的重要病因；HMGB1/mTOR通路是介导自噬调控TJ蛋白的热门通路。益气温阳方是基于中医耳鼻喉科泰斗干祖望教授治疗AR经验形成的验方，疗效确切。本项目预实验发现AR患者鼻粘膜屏障受损，AR模型中自噬蛋白表达上调，TJ蛋白表达下调。益气温阳方给药干预后可逆转其结果。据此，提出本项目科学假说：益气温阳方调控HMGB1/mTOR通路信号通路抑制自噬稳定TJ蛋白治疗AR。本项目拟以C57BL/6小鼠、HNEpC构建的AR动物、细胞模型为实验对象，运用RNA干扰、免疫荧光等技术手段，对本项目假说的机制深入探讨，以进一步明确益气温阳方治疗AR的生物学基础，诠释“正气存内、邪不可干”治则的科学内涵。

Allergic rhinitis (AR) is a common chronic otolaryngology disease closely related to impaired nasal mucosal barrier function. At present, its long-term therapeutic effect is not ideal and it is prone to recurrent attacks. Tight junction (TJ) proteins are important structures for maintaining mucosal barrier. Recent studies have shown that damage of TJ proteins lead to disruption of nasal mucosal barrier function, which is an important cause of AR. And the HMGB1/mTOR pathway is a important pathway on mediating autophagy to regulate TJ proteins. Yiqiwenyang Formula is based on the treating AR experience of Professor Gan Zuwang, a leading otolaryngologist of Chinese medicine, which has definite clinical effect. The Pre-experiment of this project showed that the nasal mucosal barrier was damaged in AR patients. And the expression of autophagy-related proteins in AR models was up-regulated, while the expression of TJ-related proteins was down-regulated. The result could be reversed after the intervention of Yiqiwenyang Formula. Accordingly, the scientific hypothesis is put forward: Yiqiwenyang Formula inhibits autophagy to stabilize TJ proteins through HMGB1/mTOR signaling pathwayin the treatment of AR. The project intends to take the AR animal model constructed by C57BL/6 mice and cell model constructed by human nasal epithelial cells (HNEpC) as the experimental objects.The RNA interference, immunofluorescence and other techniques will be used to further explore the mechanism of this hypothesis. Through this project, the biological basis of YiFengYang Formula for AR treatment will be further clarified, and the scientific connotation of the TCM treatment principle of "positive qi stored inside, evil can not violate"will be more understood.