ATRQβ-001疫苗改善糖尿病肾损伤及作用机制研究

Diabetic nephropathy (DN) is the most common cause of end-stage renal diseases. Overactivation of the renin-angiotensin system (RAS) plays a crucial role in the development of the disease. Our group has developed a therapeutic hypertensive vaccine against angiotensin (Ang) II type 1 receptor (AT1R) named ATRQβ-001, which decreased the blood pressure of hypertensive animals effectively. In our previous study, we demonstrated that ATRQβ-001 vaccine ameliorated streptozotocin-induced diabetic renal injury. Accordingly, this study is designed to further verify the effectiveness of ATRQ β-001 vaccine in experimental DN and the potential mechanisms. Our hypothesis is that ATRQ β-001 vaccine is a RAS modulator rather than a blocker. ATRQβ-001 vaccination suppresses renal Ang Ⅱ-AT1R activation and abrogated the downregulation of ACE2-Ang (1-7) with no feedback of RAS, providing a novel , safe , and promising method to treat diabetic nephropathy.

糖尿病肾病是导致终末期肾病的最常见原因，肾素-血管紧张素系统（RAS）在其发生发展中起着重要作用。我们研制出的针对人血管紧张素1型受体（AT1R）短肽疫苗ATRQβ-001，可有效降低血压。前期研究中，我们证实ATRQβ-001疫苗可以有效保护链脲佐菌素诱导的糖尿病肾病大鼠肾损害，本课题将进一步证实ATRQβ-001疫苗对糖尿病肾病模型动物的保护作用及其可能机制，并提出ATRQβ-001疫苗通过调控RAS双轴，即主要通过抑制肾脏局部ACE-AngⅡ-AT1R轴，正向调控ACE2-Ang（1-7）-Mas轴，抑制炎症细胞浸润及炎性细胞因子的表达，并且无反馈性RAS激活。同时在体外实验进一步阐述ATRQβ-001疫苗的可能作用机制。本实验将进一步验证ATRQβ-001疫苗对糖尿病肾病的保护作用，为糖尿病肾病的治疗提供新方法和新思路。