急性肾损伤（AKI）是慢性肾脏病（CKD）的独立危险因素，部分患者可最终演变为CKD或终末期肾脏病，然而其机制不清。近年研究发现肾小球毛细血管内皮细胞损伤和功能障碍在AKI-to-CKD的发生发展中发挥重要作用。我们前期的体外研究已证实，SENP1介导的HIF通路去苏素化修饰可以调节足细胞中VEGF的生成，并通过旁分泌作用保护肾小球内皮细胞抵御缺氧诱导的损伤和凋亡，促进内皮细胞的迁移并形成毛细血管网。本研究在此基础上，进一步构建大鼠AKI-to-CKD肾小球损伤模型，利用SENP1腺病毒高表达和低表达载体在体内干预SENP1的表达，探索SENP1介导的去苏素化修饰是否能够在体内调控HIF通路的活化进而阻断AKI-to-CKD进展，为阻抑AKI后肾小球病变的进展提供新的治疗策略。

Acute kidney injury (AKI) is an independent risk factor for chronic kidney disease (CKD). Some AKI patients may eventually evolve into CKD or end-stage renal disease. However, the mechanism of the progressive renal changes following AKI remains unclear. Recent studies have found that glomerular endothelial cell damage and dysfunction plays an important role in the development of AKI-to-CKD. Our previous research indicated that SENP1 was essential for activating HIF-1α pathway and VEGF secretion in cultured podocytes, which subsequently protected co-cultured glomerular endothelial cells from hypoxic induced injury and apoptosis. In this study, we plan to establish a rat model imitating the pathological changes of glomeruli during AKI-to-CKD in vivo. Using the SENP1 short hairpin RNA (shRNA) recombinant adenovirus vector and SENP1 DNA recombinant adenovirus vector, we will create SENP1-knockdown and SENP1 overexpression AKI-to-CKD rat models. We hope to verify that SENP1 mediated HIF deSUMOylation is an important point regulating the immunological changes, inflammatory reactions, oxidative stress, and glomerular sclerosis induced by acute kidney injury. Our findings should provide a new strategy for the treatment of the glomerular changes and dysfunction during the process of AKI-to-CKD.