以YAP为靶向的复方血栓通治疗糖尿病视网膜病的物质基础与药理机制研究

糖尿病视网膜病（DR）是各型糖尿病的晚期并发症，患病率高，危害大。复方血栓通作为国家二级中药保护品种，活血化瘀，益气养阴，治疗DR疗效显著，但是其具有中药复方的典型局限性，即物质基础与药理机制不清，导致其临床应用价值被严重制约。文献调研发现血管增生是DR的标志性事件，YAP作为转录辅助因子，是血管增生的核心机制。而且课题组证实，复方血栓通通过靶向YAP调控血管增生，从而达到治疗DR的效果。本课题拟以YAP为靶蛋白，采用超滤质谱技术筛选复方血栓通效应分子（群）；以此为基础，利用网络药理学技术阐明效应分子（群）以YAP为核心的靶标；结合经典的细胞生物学及分子生物学实验验证，构建效应成分-靶标分子-信号通路-疾病网络，最终明晰复方血栓通以YAP为靶向的治疗DR的物质基础及药理机制。本课题不仅为研究中药复方的物质基础和药理机制开发了新颖的研究范式，而且对于其他血管增生性疾病的药物开发具有重大意义。

Diabetic retinopathy (DR) is a complication in the late stage of various types of diabetes with high incidence and great risk. Fufang Xueshuantong (FXST), which can activate blood, remove stasis, nourish qi and Yin, is one of the Protection of Varieties of Traditional Chinese Medicines. FXST is effective in treatment of DR, but its material basis and pharmacological mechanisms are not clarified. This leads to the constraint on the clinical use of FXST. Literature indicates that angiogenesis is the key characteristics of DR, and YAP is the core component of angiogenesis. Moreover FXST inhibited angiogenesis and treated DR through targeting YAP. Thus the aim of this study is to choose YAP as the target protein and screen the effective constituents by ultrafiltration mass spectrometry. On the basis of this, the network pharmacological technology will be used to illustrate the target proteins which interact with YAP. In combination with the cell biology and molecular biology, the network which includes effect components - the target molecules - signalling pathway - disease will be constructed. In the end these results will bring light to the material basis and pharmacological mechanisms of FXST. This project will develop a new paradigm for the material basis and pharmacological mechanism research of traditional Chinese medicine. And it is of great value for the development of new drugs for other diseases with angiogenesis.