藏药勇哇西汤调控DN血管内皮网络稳态的配伍机制研究

项目名称： 藏药勇哇西汤调控DN血管内皮网络稳态的配伍机制研究

项目编号： No.81473427

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： 赖先荣

作者单位： 成都中医药大学

项目金额： 71万元

中文摘要： 微血管内皮损伤是糖尿病肾病（DN）的中心环节，前期基金研究发现小檗皮对糖尿病微血管内皮有保护作用，调控相关的PKC、HIF、VEGF等多靶点网络。藏医认为DN病缘为培根、脂肪增长不能转化，治法用勇哇西汤（小檗皮等四味藏药组方）内服，有抑制微血管通透性增高等作用，而《四部医典》有药无量、现代制剂量效关系不明确，在此基础上，本项目提出假说勇哇西汤防治DN存在量效配伍，与多靶点调控血管内皮网络稳态有关，拟采用均匀设计-偏最小二乘及灰色关联等分析，应用STZ诱导DN模型、自发性DN模型、高糖DN微血管细胞内皮模型，UFLC-UV/MS等手段分析血清指纹图谱及变化特征，高分辨彩超及全自动生化测定等技术检测血管内皮功能、肾功能，与RT-PCR、Western免疫印迹及免疫组化等生物技术结合，探索多药味量效配伍对PKC、HIF、VEGF、Ang、TGF等DN血管内皮网络的多靶点调控机制，以发挥藏医药防治糖尿病的优势。

中文关键词： 藏药；勇哇西汤；糖尿病肾病；血管内皮网络稳态；配伍机制

英文摘要： Microvascular endothelial injury is the central link in diabetic nephropathy (DN), early prevention is the key, effective of single-target was limitations. Prophase NSFC projects research had found the manifest protection effective for diabetes microvascular endothelial using Berberis Cotex, associated with vascular endothelial network regulation by multiple-targets (such as PKC and HIF and VEGF and etc.) with multiple-components. Based on the tibetan medicine theory that cause of DN disease was growth of the Phlegm and the Fat can not be converted, detailed treatment was using Siwei Jianghuang Soup (prescription with Berberis Cotex and other three herba drugs) orally, which can inhibit capillary permeability and etc., but in the classics of tibetan medicine theory, The Four Medical Classics, was not record the dosage for each drug, and the relationship between doseage and effect of the modern preparation Siwei jianghuang Soup was not clear yet, on this basis, this project put forward the hypothesis that An amount-effective compatibilities should present for Siwei Jianghuang Soup to treatment DN, associated with multi-components and multi-targets regulation of vascular endothelial network stability, intends to adopt Uniform Design(UD)-Partial Least Squares Analysis (PLSA) and Grey Correlation AnalysisI(GCA) and etc., application STZ-induced DN model and spontaneity DN model and high-sugar foster DN cell model, UFLC-UV/MS and other Methods to analysis the serum fingerprinting and its variation characteristics before and after administration, medical testing methods such as high-resolution colored ultrasound technology and Full automatic biochemical analyzer to accurately reflect the vascular endothelial function and renal function (UAER, UA), biological technologies such as RT-PCR and Western blot to detect vascular cytokines, such as PKC and HIF and VEGF and Ang and NO and TGF and etc., exploring the multiple-targets regulatory mechanisms for vascular endothelial networks stability with multiple-compatibility-components associated PKC and HIF and VEGF and Ang and NO and etc., in order to increase scientific evidence for predominance and characteristics of diabetes treatment with Tibetan medicine.

英文关键词： Tibetan medicine;Siwei Jianghuang Soup;Diabetic Nephropathy;vascular endothelial network stability;Synergetic mechanism