Acute lung injury (ALI) is one of the most severe outcomes of sepsis which still waiting for effective treatment method. Roxadustat (FG-4592) which is often used for treatment of anemia in patients with chronic kidney disease (CKD), its affection on LPS-induced ALI haven’t been evaluated. MH-S and MLE-12 cell injury and ALI mouse model was induced LPS. Several assays were used to explore the role of FG-4592 in reducing the damage caused by LPS. FG-4592 treatment significantly upregulated HIF-1α and HO-1 and strikingly attenuated inflammation in vivo and in vitro. Furthermore, septic mice overexpressing HIF-1α had high level of survival rate and lower expression of inflammatory factors while down-regulation can enhance the damage of LPS. HIF-1α has a protective effect on acute lung injury in LPS induced septic mice. FG-4592 treatment remarkably ameliorated the LPS-induced lung injury through the stabilization of HIF-1α. Besides the role in treating CKD anemia, the clinical use of FG-4592 also might be extended to ALI.

急性肺损伤（ALI）是脓毒症最严重的后果之一，尚待有效的治疗方法。Roxadustat (FG-4592) 常用于治疗慢性肾脏病 (CKD) 患者的贫血，尚未评估其对 LPS 诱导的 ALI 的影响。MH-S和MLE-12细胞损伤和ALI小鼠模型被LPS诱导。使用了几种检测方法来探索 FG-4592 在减少 LPS 造成的损害中的作用。FG-4592 治疗显着上调 HIF-1α 和 HO-1 并显着减弱体内和体外的炎症. 此外，过度表达 HIF-1α 的脓毒症小鼠具有较高的存活率和较低的炎症因子表达，而下调可以增强 LPS 的损伤。HIF-1α对LPS诱导的脓毒症小鼠急性肺损伤具有保护作用。FG-4592 治疗通过稳定 HIF-1α 显着改善 LPS 诱导的肺损伤。除了在治疗 CKD 贫血中的作用外，FG-4592 的临床应用也可能扩展到 ALI。