补肾益气通络化浊法经PKC通路治疗糖尿病肾病的作用及机制研究

项目名称： 补肾益气通络化浊法经PKC通路治疗糖尿病肾病的作用及机制研究

项目编号： No.81460699

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张定华

作者单位： 甘肃省中医院

项目金额： 50万元

中文摘要： 糖尿病肾病（DN）是终末期肾病首位病因。研究发现，细胞间隙连接蛋白43（Cx43）在肾脏多种细胞表达，且在DN发病与进展中起重要作用，高糖通过蛋白激酶C（PKC）高度磷酸化Cx43导致其下调，引起肾脏系膜细胞肥大、肾小球高灌注发生DN。课题组前期研究发现，具有补肾益气通络化浊作用的中药复方糖肾康能改善DN大鼠肾脏高滤过、细胞外基质积聚、细胞肥大等病理变化，且发现糖肾康可明显上调DN大鼠肾脏Cx43表达。据此提出糖肾康可能通过PKC通路调控Cx43防治DN假说。课题以Cx43为切入点，以PKC信号途径为主线，采用国际公认的SV40 MES 13肾小球系膜细胞模型、CD57BL/6肾小管上皮细胞模型及db/db小鼠动物模型，从一个新的视角，在整体-细胞-分子不同层次上，研究糖肾康对DN作用及可能的分子调控机制，以期为DN的中药治疗提供理论和实验依据。

中文关键词： 补肾益气通络化浊法；糖尿病肾病；蛋白激酶C通路；间隙连接蛋白43

英文摘要： Diabetic nephropathy (DN) is the first cause of end-stage renal disease. The study found,connexin 43 (Cx43) expression in renal cells, and plays an important role in the pathogenesis and development of DN, high glucose phosphorylated highly Cx43 leading to its down regulation by protein kinase C (PKC) ，and then Cause renal mesangial cell hypertrophy, glomerular hyperfiltration in DN.In the experimentally we observed in Tangshenkang could markedly up-regulate the mRNA and protein expression of DN Cx43 in kidney of rats. We put forward the Hypothesis that Tangshenkang prevent and treatment diabetic nephropathy through regulating the PKC pathway and up-regulation of Cx43. Our group will take Cx43 and PKC passway as a target to research that tangshenkang how to regulate PKC passway，ploing the cell model of SV40 MES 13 mesangial cells、CD57BL/6 renal tubular epitClarify the mechanismshelial cell and the animal models of db/db mouse,what had recognized by the world，from the whole - cell - molecular level,And then clarify the mechanismsem that tangshenkang raise Cx43,Reveal the new target for the method of Kidney tonifying，Qi Supplementing，Collateral Dredging，Turbidity Dissolving treamenting DNProvide new ideas for Chinese medicine treatment of DN.

英文关键词： the method of Kidney Tonifying;Qi Supplementing;Collateral Dredging;Turbidity Dissolving;Nephropathy Diabetic;Protein kinase C pathway;Connexin 43