Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, China.
Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, China.
Respir Physiol Neurobiol. 2020 Oct;281:103506. doi: 10.1016/j.resp.2020.103506. Epub 2020 Jul 26.
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，目前仍缺乏有效的治疗方法。罗沙司他（FG-4592）常用于治疗慢性肾脏病（CKD）患者的贫血，但其对脂多糖（LPS）诱导的 ALI 的影响尚未得到评估。本研究采用 LPS 诱导 MH-S 和 MLE-12 细胞损伤及 ALI 小鼠模型，探讨 FG-4592 减轻 LPS 损伤的作用。结果显示，FG-4592 治疗可显著上调 HIF-1α 和 HO-1，显著减轻体内外炎症。此外，过表达 HIF-1α 的脓毒症小鼠存活率较高，炎症因子表达较低，而下调 HIF-1α 可加重 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 通过稳定 HIF-1α 显著改善 LPS 诱导的肺损伤。除了在治疗 CKD 贫血方面的作用外，FG-4592 的临床应用也可能扩展到 ALI。
