从调控上皮细胞易感性探讨玉屏风散益气固表防治过敏性疾病的机制

益气固表方玉屏风散广泛用于过敏性疾病，结合过敏性疾病的现代认识及前期工作基础，提出假说：玉屏风散通过调控上皮细胞易感性，抑制促过敏微环境的形成，从而改善过敏体质、控制疾病进程并减少复发；该效应是由作用于上皮细胞的成分群通过影响模式识别受体PRRs相关通路及细胞间连接的结构蛋白而实现的。研究1）玉屏风散对整体过敏性疾病模型中上皮细胞易感性的影响；2）玉屏风散及单体成分对离体上皮细胞PRRs通路和细胞连接蛋白的影响，提示其可能的机制；3）针对上述发现的玉屏风散成分群产生影响的关键分子群，采用特异性抑制剂或基因沉默等干预手段，在离体上皮细胞及整体模型上，考察分子在YPFS效应机制中的作用，验证成分群作用的主要通路和靶分子。4）分析玉屏风散多成分多靶点调控上皮细胞易感性的作用机制。通过以上研究试图阐明玉屏风散多成分多靶点防治过敏性疾病的机制与调控上皮细胞易感性的相关性，探索益气固表治病求本的内涵。

Current therapy for allergic diseases only manage symptoms and do not alter the natural course of disease. Yu-ping-feng-san(YPFS), a typical formulae of Yi-qi-gu-biao method in Chinese medicine, can alter the natural course of disease and prevent the recurrence of the allergic diseases in clinic. Improved understanding of the epithelium's susceptibility to environmental insults in allergic diseases has provided important mechanistic insight into how allergy is initiated and perpetuated. Our previous study showed that Th2 mediated allergic contact dermatitis(ACD)was inhibited and epithelial cell(EC) derived TSLP was significantly reduced by YPFS.Moreover,epithelial cell extraction combined with HPLC-MS was used to screen potential chemicals which can bind to ECs and five chemicals were found out. Herein, the hypothesis is proposed that the Yi-qi-gu-biao mechanism of YPFS is closely related to regulation of EC's susceptibility with ameliorating PRRs activation and epithelial barriar defect by active components in YPFS. To verify this, the following research would be conducted. Firstly, the effect of YPFS on susceptibility of ECs(PRRs related pathway and epithelial barrier protein) in mice OVA induced asthma and FITC induced ACD would be explored in vivo. Then we will study the effect of YPFS and its ingredients on PRRs activation,integrity of ECs and related signaling pathway in vitro. With some key factors being illustrated, the inhibitor, antibody or RNAi would be employed to demonstrate the role of these molecules in the effect of YPFS. Finally,the network of multi-component and multi-targets effect of YPFS will be analysed by software cytoscape. Through this study, it is expected that the regulatory mechanism of YPFS on susceptibility of ECs could be revealed and this would explain how the Yi-qi-gu-biao method works. In addition, potential new targets might be raised by this research.