基于病理网络多靶标的丹皮多组分防治糖尿病肾病的整合调节机制研究

项目名称： 基于病理网络多靶标的丹皮多组分防治糖尿病肾病的整合调节机制研究

项目编号： No.81473394

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 封亮

作者单位： 南京中医药大学

项目金额： 75万元

中文摘要： 糖尿病肾病(DN)是源于高血糖引发的多环节、多层次病理特征的糖尿病微血管并发症，目前临床治疗措施已经从传统的单分子或单靶点向多药物成分和多靶点途径转变，这与中药整体观内涵相吻合。本项目在牡丹皮防治DN药效评估和成分筛选的基础上，基于血液-内皮-系膜的病理网络特点，通过UPLC-Q-TOF/MS色谱分析手段，揭示丹皮多组分(萜苷、鞣质等)抑制DN大鼠血液糖基化产物的化学机制；采用多重分子和蛋白数据库、信号通路软件以及数据整合平台等网络药理学方法，结合cDNA基因芯片等生物信息学技术分析DN大鼠肾脏的基因、蛋白表达差异，从整体到局部揭示丹皮多组分干预DN的总体生物信息网络和血液、内皮、系膜各部位的生物信息网络，最终阐明丹皮多组分通过多靶点、多环节、多层次防治DN的整合调控机制，为创新组分结构中药的作用机理研究提供新的模式和方法。

中文关键词： 糖尿病肾病；网络药理学；多组分；整合调节机制；多靶标

英文摘要： Diabetic nephropathy (DN), one of microvascular complications of diabetes mellitus, was caused by hyperglycemia with complex, multi-facetted and multi-level pathological features. Current clinical treatment has shifted from the traditional single drug molecule and single target to multiple drugs and multiple targets, which is consistent with the overall concept of the connotation of Chinese medicine. Based on the efficacy assessment and components screening of Mudanpi on the prevention and treatment of DN in our previous project, the present project was performed in the light of the pathological network characteristics of Blood - Endothelium - Mesangial. In this project, UPLC-Q-TOF/MS chromatographic analysis was performed to reveal the chemical mechanism of Mudanpi multicomponent (terpene glycosides, tannins, etc.) on inhibiting glycation products in blood of DN rats. Most importantly, network pharmacology methods including multiple molecular and protein databases, signaling pathways software and data integration platform, were conducted to analyze the expression difference of genes and proteins in kidney tissue of DN rats through combining with cDNA microarray bioinformatics, etc. The overall bioinformatics network and the individual bioinformatics networks of blood, endothelial, mesangial of kidney were established from the integrity to each section to clarify ultimately the integrated regulatory mechanisms of the multi-components of Mudanpi on the prevention and treatment of DN with multi-target, multi-facetted, multi-level characteristics. This investigation provides a novel model and method for the study on action mechanism of the innovative structural components of Chinese medicine.

英文关键词： Diabetic nephropathy;network pharmacology;multi-component;integrated regulatory mechanisms;multi-target