内皮功能障碍（EDF）在糖尿病肾病（DN）发病中具有重要作用，四氢生物喋呤（BH4）作为eNOS的必需辅因子，其含量降低导致的eNOS脱偶联和NO生物利用度降低，是引起EDF的关键因素。前期研究发现：调节BH4含量的关键酶QDPR在DN中发生了明显改变，但其在DN中的作用尚未见报道。已获得临床批件的柴黄益肾颗粒能逆转DN大鼠QDPR的下调。基于此发现，本研究拟利用定量PCR、Western blot及流式细胞等技术，结合动物及细胞实验，通过重组质粒及siRNA转染方法，分析QDPR/BH4途径、eNOS脱偶联及EDF改标志分子改变与DN病变的关系，揭示QDPR/BH4途径在DN中EDF的作用及柴黄益肾颗粒的调控机制，并利用萤光素酶报告基因系统明确柴黄益肾颗粒调节QDPR启动子的特定区域。本研究对于DN药物新靶标的发现及柴黄益肾颗粒治疗DN分子机制及生物学内涵的阐释，具有重要意义。

Endothelial dysfunction（EDF） plays an important role in the pathogenesis of diabetic nephropathy（DN）. As an essential cofactor required for eNOS activity, BH4 with a decreased level is a major factor of EDF by leading to eNOS uncoupling and consequent loss of NO bioavailability. Our previous studies has firstly revealed the abnormality of QDPR in DN, which is critical in regulating BH4 level. Changhuang-Yishen Granule(CHYS) could reverse the downregulation of renal QDPR expression in DN.However, the role of QDPR in DN remains to be clarified. In this study, we plan to observe the changes of QDPR/BH4 pathway and eNOS/NO and ETF marker under the condition of DN.Then we will analyse the relationship of these changes and renal injury with both in vitro and in vivo experiments. Furthermore,we plan to clarify the role of QDPR/BH4 mediated EDF in DN pathogenesis by utilizing plasmid transfection and siRNA technology and then investigate the intervention of CHYS on the pathway. Finally,we plan to identify the target zone of CHYS on the regulation of QDPR promoter by luciferase reporter genes system. The research will exhibit important significance in exploring the new target of drugs in DN, and revealing the molecular mechanism and biological connotation of CHYS in treating DN.