ALR通过STAT3/System Xc- 途径对急性肾损伤中铁死亡的干预作用及机制研究

急性肾损伤（AKI）是临床常见的危急症，有较高的发病率和病死率。最近研究发现肾小管上皮细胞（RTEC）铁死亡是AKI的重要发病机制，但有待进一步阐明。铁死亡的本质是谷胱甘肽过氧化物酶4（GPX4）活性下降，造成脂质活性氧（ROS）的积累导致细胞死亡。胱氨酸/谷氨酸反向转运体（System Xc-）通道是调节GPX4活性的关键，STAT3可以负向调控System Xc-的活性。 . 我们前期研究发现肝再生增强因子（ALR）具有促进RTEC增殖、抑制RTEC凋亡的作用；同时发现ALR可以抑制RTEC产生ROS，但具体机制不清楚。我们最近发现体外干扰ALR的表达可以加重RTEC铁死亡，而ALR对STAT3具有调控作用，因此，我们提出科学假说：ALR可能通过干预RTEC铁死亡而对AKI发挥肾保护作用，其作用途径可能与ALR抑制STAT3的表达，从而调控System Xc-介导的胱氨酸代谢有关。

Acute kidney injury (AKI) is a common and severe renal disease characterized by high morbidity and mortality. Recent studies have found that ferroptosis of renal tubular epithelial cell was involved in AKI .However, the mechanism remains to be clarified at present . The essence of ferroptosis is metabolic disorder of lipid oxide, thus lipid peroxides can not get through GSH metabolism catalyzed by GPX4, which produces a large amount of toxic lipid ROS. Morever, the decrease in the activity of System Xc- induced aboundant accumulation ROS is the key to trigger ferroptosis. STAT3 could negatively regulate System Xc- expression recently. . Our preliminary data revealed that Augmenter of liver regeneration(ALR) has protective effect on acute kidney injury by inhibiting apoptosis and regulating autophagy in renal tubular epithelial cell .We also found that ALR has a protective effect on AKI by ameliorating the production of ROS. However, the mechanism is blurred. ALR could regulate STAT3. We also found that renal tubular epithelial cell could cause more severe ferroptosis through interfering ALR expression. So, We suggest that ALR shows protective effect on ferroptosis through regulates System Xc- mediated cystine metabolism by STAT3 signal pathway.