肾脏纤维化是慢性肾脏病发展至终末期肾脏病的共同通路。我们前期研究Renalase抗肾纤维化过程中发现高表达的内质网应激有明显下调；研究显示后者可上调参与肾纤维化的GSK-3β/Snail通路，推测Renalase通过抑制内质网应激下调GSK-3β/Snail延缓肾纤维化。本研究首先利用单侧输尿管结扎（UUO）大鼠模型明确在肾纤维化过程中Renalase与内质网应激、GSK-3β/Snail的表达关系。然后应用肾小管上皮细胞及UUO大鼠模型，首先应用化学制剂激活及抑制内质网应激；其次在细胞水平构建GSK-3β质粒及siRNA，在动物水平构建GSK-3β过表达及低表达腺病毒激活及抑制GSK-3β/Snail，明确内质网应激、GSK-3β/Snail通路在Renalase抗肾纤维化中的作用及上下游关系，揭示Renalase抗肾纤维化的机制，以期为临床延缓肾纤维化治疗提供新的实验室依据。

Renal fibrosis is a common pathway for progression of chronic kidney disease to end-stage renal disease. However，there is no effective method against renal fibrosis in clinic. Our previous work showed that Renalase could delay renal fibrosis and endoplasmic reticulum stress was involved in this process，which can be down-regulated by Renalase. Combined with previous studies showing that endoplasmic reticulum stress can regulate the GSK-3β/Snail signaling pathway which involved in renal fibrosis, we hypothesized that Renalase could down-regulate the GSK-3β/Snail signaling pathway by inhibiting endoplasmic reticulum stress, thereby delaying renal fibrosis. In this study, we firstly identified he relationship between Renalase and endoplasmic reticulum stress and the GSK-3β/Snail signaling pathway by histological and molecular biology techniques during renal fibrosis in unilateral ureteral occlusion(UUO) rats. Then, respectively in vitro and vivo, we applied chemical activation and inhibition of endoplasmic reticulum stress and used adenovirus transfection, plasmid transfection, siRNA technology to active and inhibit GSK-3β/Snail signaling pathway successively to clarify the role of endoplasmic reticulum stress and GSK-3β/Snail signaling pathway in Renalase's anti-renal fibrosis and its up- and down-stream relationship, so as to reveal that Renalase down-regulates the GSK-3β/Snail signaling pathway by inhibiting endoplasmic reticulum stress to delay renal fibrosis. This project intends to provide new insights for the role of Renalase in renal fibrosis and search for novel therapeutic strategies.