急性肾损伤（AKI）是慢性肾脏病（CKD）的独立危险因子；AKI-CKD转化是AKI预后不良的主要决定因素；抑制AKI-CKD转化是亟待解决的科学问题；巨噬细胞亚型极化是参与AKI-CKD转化的关键环节之一。申请人前期工作发现SerpinC1/ATIII是影响巨噬细胞极化的重要基因之一，与AKI-CKD转化有关；本项目假设其机制为：SerpinC1/ATIII通过直接或间接信号作用于巨噬细胞，抑制巨噬细胞向M1极化并促进其向M2极化，最终抑制AKI-CKD转化。申请人将利用SerpinC1敲除与M2巨噬细胞减灭方法进行体内实验与体外实验，探讨SerpinC1/ATIII直接作用于巨噬细胞，或通过前列腺素I2间接作用于巨噬细胞，调节巨噬细胞极化从而抑制AKI-CKD转化的分子机制，为临床AKI-CKD转化防治提供思路。

Acute kidney injury (AKI) is an important risk factor of chronic kidney disease (CKD). AKI-CKD transition is the main determinant of AKI prognosis and how to suppress AKI-CKD transition has become a hotspot in AKI research. Macrophage polarization is critically involved in AKI-CKD transition and the applicants recently found that SerpinC1/Antithrombin III is the key gene that regulates the macrophage polarization and is closely associated with AKI-CKD transition. We hypothesize that SerpinC1/Antithrombin III inhibits AKI-CKD transition via inhibiting M1-like macrophage polarization and prompting M2-like macrophage polarization directly or indirectly. By using SerpinC1 knockout and M2-like macrophage depletion, experiments in vivo and in vitro will be performed to elucidate the molecular mechanism underlying SerpinC1/Antithrombin III’s effects on prompting M2-like macrophage polarization and suppressing AKI-CKD transition and determine whether these beneficial effects are mediated by directly acting on macrophage or indirectly up-regulating PGI2. Thus, this study will provide us a novel approach to prevent AKI-CKD transition.