急性肾损伤（AKI）为临床常见疾病，且预后不良，易发展成慢性肾脏疾病（CKD），微血管内皮损伤是它们共同的病理改变、贯穿于在它们发生、发展过程，并在肾小管间质纤维化逆转中也起关键作用，有关血管生成素系统特别是从受体水平、核心环节Tie2信号在其中的作用的相关研究有限，本项目利用小鼠叶酸肾病早期急性肾损伤和后继慢性肾小管间质纤维化这个模型，且均存在微血管内皮损伤，先研究Tie2 信号激活对微血管内皮细胞的保护作用以及相应的在急性肾损伤和后继的慢性肾小管间质纤维化发生中的防治作用,另一个研究是在形成慢性肾小管间质纤维化基础上，探讨Tie 2 信号激活促进纤维化区毛细血管再生来逆转这个过程，并在体外实验研究其微血管保护的相关机制，为微血管内皮及Tie2信号损伤在急性肾损伤和后继的慢性肾小管间质纤维化中的作用提供理论依据，也为防治急性肾损伤后慢性肾脏病的发生、甚至逆转提供新的靶分字。

Acute Renal injury (AKI) is the prevalent diseases with poor outcome and predisposed to the chronic kidney disease(CKD).The key factor - microvascular injury participated in the common pathologic process of AKI，CKD and also regression of CKD.It is still unclear about the actions of angiopoietin system on AKI and CKD，especially in the level of anchor receptor Tie 2 signal. A mouse microvascular model with endothelial injury from folic acid nephropathy will be used ，which presented AKI in the early stage and chronic renal tubulointerstitial fibrosis in the later stage .First research will use Tie 2 signal agonist to confer protective functions for microvascular endothelium and consequent therapeutic effects on the AKI and followed tubulointerstitial fibrosis. Then on the basis of formed renal tubulointerstitial fibfosis，another study will explore the effects of Tie 2 signal agonist on the regression of tubulointerstitial fibrosis through stimulation of pretubule capillary growth of fibrosis area. Underlying mechanisms will also be discovered by experiments in vitro. These promising studies will provide new information on the theoretic development of microvascule and Tie 2 signal injury involved in the AKI and CKD. Tie 2 signal might be as a new potential target for prevention and even regression of chronic renal tubulointerstitial fibrosis after AKI.