糖尿病肾病是成人慢性肾功能衰竭的主要病因之一。我们在国际上率先研制出人血管紧张素1型受体（AT1R）短肽疫苗ATRQβ-001，有效降低血压，更好保护靶器官；在研发过程中，我们发现ATRQβ-001疫苗不仅具有RAS阻滞作用，还具有RAS调节作用。因此，本课题将研究ATRQβ-001疫苗对糖尿病肾病大鼠保护作用，并提出假说：1）疫苗抗体与AT1R结合，通过阻碍受体变构抑制受体活化，促进AT1受体内化降解，抑制肾脏内皮细胞和系膜细胞生成AngⅡ；2）抑制循环和肾脏局部ACE-AngⅡ-AT1R轴，同时激活ACE2-Ang(1-7)-MasR轴，避免AngⅡ浓度和肾素活性反馈增加，发挥RAS调节作用。本实验将阐明ATRQβ-001疫苗对糖尿病肾病的保护机制，为糖尿病肾病治疗提供新方法和新思路。

Diabetic nephropathy (DN) is one of the main causes of chronic renal failure in adults. In our previous study, we have developed a short peptide vaccine ATRQβ-001 against angiotensin type 1 receptor(AT1R), which can effectively reduce blood pressure and protect target organs. We found that ATRQβ-001 vaccine is not a simply blocker but a novel regulator of RAS system. Our hypothesis is that the antibody created by ATRQβ-001 vaccine immunization binds to AT1 receptor and inhibits receptor activation by blocking receptor allosteric transition and then promotes AT1 receptor internalization degradation. Meanwhile, the production of AngⅡfrom renal endothelial cells or mesangial cells is decline. After the immunization, ACE-AngⅡ-AT1R axis is inhibted but an activation of ACE2-Ang1-7-MasR at the same time, which can improve the target organ protection and avoid the feedback activation of renin-angiotensin Ⅱ system. This study is trying to explore the protection effect of ATRQβ-001 vaccine in DN and reveals its mechanism and finally find a new way in the treatment of DN.