补体异常激活加重肾缺血再灌注损伤（IRI），补体抑制剂CRIg/FH减轻炎性损伤，但其促修复机制仍未阐明。我们前期发现CRIg/FH结合C3b，减轻肾小管上皮细胞（RTECs）氧化应激，并活化PI3K-Akt缓解肾IRI；CRIg/FH抑制RTECs氧化应激相关Pkc/Rac1/ROS，下调Dnmt3a/3b；CRIg/FH促进RTECs血小板源性生长因子（PDGF-BB）表达；Pdgfb启动子CpG岛丰富，为甲基化潜在靶点。故推测：CRIg/FH抑制补体激活和RTECs氧化应激，下调DNMT3A/3B，导致Pdgfb启动子去甲基化，促进PDGF-BB表达，活化PDGFRβ及PI3K-Akt，减少凋亡并促进肾修复。项目以CRIg/FH抑制IRI补体激活相关氧化应激为基础，结合启动子甲基化调控和条件敲除鼠，阐明CRIg/FH缓解肾IRI新机制，为防治IRI提供免疫学和表观遗传学交叉的新思路。

The aberrant activation of complement cascade exacerbates the renal ischemia reperfusion injury (IRI). Though CRIg/FH, a novel complement inhibitor, may ease the inflammatory injury, the mechanism of its rehabilitative role in IRI has not been fully elucidated. Our previous data has shown that the interaction between CRIg/FH and C3b, could reduce the oxidative stress in renal tubular epithelial cells (RTECs), and activate PI3K-Akt signaling to alleviate renal IRI. Moreover, CRIg/FH could inhibit oxidative stress relevant activation of Pkc/Rac1/ROS and downregulate Dnmt3a/3b. Additionally, CRIg/FH promotes the expression of platelet-derived growth factor (PDGF-BB) in RTECs. And the promoter of Pdgfb has been recognized with several CpG-riched sequences, suggesting a methylation-related regulation mechanism. Herein, we propose that, CRIg/FH could inhibit the activation of complement system and oxidative stress in RTECs, and then downregulate the expression and activity of DNMT3A/3B. The deactivation of DNMT3A/3B may give rise to the demethylation of Pdgfb promoter, and facilitate the expression of PDGF-BB. Hereafter, the PDGFRβand downstream PI3K-Akt signaling are further activated, and the cell apoptosis has been decreased to improve the recovery of kidney. Based on our previous work that CRIg/FH exerts therapeutic effects through the inhibition of IRI complement activation-related oxidative stress, combining series of molecular techniques such as promoter methylation regulation and conditional knockout mice, this project will explore a new mechanism of CRIg/FH in alleviating renal IRI, which will provide a new insight into the prevention and treatment of IRI through the cross-talk between immunology and epigenetics.