血管紧张素转换酶（ACE）与缓激肽受体（BR）基因影响糖尿病肾病（DKD）进程。已知ACE基因II比DD型对ACEI反应显著，DKD者蛋白尿分别下降51.5%和7.7%。我们前期研究表明，培哚普利（一种ACEI）联合胰激肽原酶可显著降低DKD者蛋白尿，改善模型鼠足细胞损伤。但这两种药物的协同机制，特别是ACE基因多态性与BR组合的内在联系却鲜见研究。故提出假说：ACE基因II型与B2R组合型，可激活BR受体下游信号，缓解病程，达到协同效应。为验证该假说，本研究通过转基因技术，建立ACE基因II、ID与DD型DKD模型，采用肾小球电镜、免疫组化，流式细胞术，激光共聚焦，实时定量PCR，电泳凝胶流动转移实验，Western免疫印迹，及放射免疫等方法，从分子、细胞和动物模型水平探讨ACE多态性与BR组合对DKD预后的机制，以及不同基因型对ACEI、胰激肽原酶干预的差异，为DKD治疗提供新的思路。

The gene polymorphism of angiotensin converting enzyme (ACE) and bradykinin receptor (BR) influence the progression in diabetic kidney disease (DKD). The study demonstrated that the response to ACE inhibitor (ACEI) for DKD patients with ACE genotype II was better than that with the genotype DD in decreasing the urinary albumin excretion (UAE), 51.5% and 7.7%, respectively. In the previous study, we found that an ACE inhibitor, Perindopril treatment with kallidinogenase significantly reduced the UAE in DKD patients, and ameliorate the podocytes damage in DKD mice model. Unfortunately, the mechanisms of the synergistic effects between the two drugs, and especially the internal relations among the gene ACE polymorphism and BR receptor remains unclear. Therefore, we raised the hypothesis that the genotype ACE II and B2R can activate the downstream signaling pathways, then alleviate the disease progression and reach the synergistic effects. In order to test the hypothesis, we intend to establish the genotype ACE II, ID and DD DKD mouse model by transgenic technology, then discuss the pathogenesis of this genotype for DKD prognosis in molecular, cellular and animal model levels by electronic microscopy, immunohistochemistry, flow cytometry, laser-confocal microscopy, real time fluorescent quantitative polymerase chain reaction, electrophoretic mobility shift assay, western immunoblotting, and radioimmunoassay.