TRIB3基因表达对糖尿病大血管致纤维病变的作用及中药桃仁干预机制研究

项目名称： TRIB3基因表达对糖尿病大血管致纤维病变的作用及中药桃仁干预机制研究

项目编号： No.81473685

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： 王军

作者单位： 天津中医药大学

项目金额： 74万元

中文摘要： 前期研究发现：糖尿病足患者大血管病变以内膜纤维性沉积、中膜纤维性增生为主；糖尿病鼠大血管病变亦与纤维化相关。中药加味桃核承气汤对血管纤维病变有显著改善作用。现为探讨大血管纤维病变与TRIB3基因表达的关系，我们提出：高糖与慢性炎症刺激引起TRIB3基因表达异常及TLR-2、TLR-4表达上调，进而激活致纤维化JNK、MARK和ATK信号传导通路，终致动脉纤维病变科学假说。采用糖尿病血管纤维病变大鼠模型，在基因、分子层面应用PCR、免疫组化、原位杂交等技术，以TRIB3基因对细胞外基质（ECM）的调控为切入点，从TLR2 、TLR4表达，JNK、MARK和ATK信号传导通路等方面，多角度进行ECM降解失衡的机制研究，来阐明糖尿病血管纤维病变的机理；进一步探讨中药桃仁于成模前及纤维化后，对致纤维化细胞因子的生成及调控，抑制ECM过度沉积等方面的作用靶点。

中文关键词： 基因表达；信号通路；糖尿病大血管纤维化；桃仁；分子机制

英文摘要： Preliminary findings : macrovascular diabetic foot to intimal fibrous deposition, fibrous membrane hyperplasia ; macrovascular diabetic rats also associated with fibrosis. Recipe for THCQT vascular fibrosis significant improvement. Explore the relationship is now with TRIB3 vascular fibrosis gene expression , we propose : High sugar and chronic inflammation caused TRIB3 abnormal gene expression and TLR-2, TLR-4 expression, which in turn activates fibrosing JNK, MARK and ATK signal transduction pathways , which ultimately caused the arterial fibrosis scientific hypothesis. Using a rat model of diabetic vascular fibers in genetic , molecular level application PCR, immunohistochemistry and in situ hybridization techniques to TRIB3 gene for extracellular matrix (ECM) of the regulation as a starting point , from TLR2, TLR4 expression , JNK aspects , MARK and ATK signal transduction pathways , and many more angles imbalance ECM degradation mechanism to clarify the mechanisms of diabetic vascular fibrosis ; further investigate the effects of walnuts into the mold before and after fibrosis, the generation of cytokines induced fibrosis and regulation , inhibition of excessive ECM deposition and other aspects of the role of target.

英文关键词： Gene expression;Signal pathway;Diabetic vascular fibrosis;Peach kernel;Molecular mechanism