Ma Wentong, Zhou Jingxin, Qian Ying, Zhang Su, Han Chuanlu, Su Jing, Sun Haijun
Department of intensive care unit, Suqian first people's Hospital, the Affiliated Suqian First People's Hospital of Nanjing Medical University, 120 suzhi Road, Sucheng District, Suqian, Jiangsu Province, 223800, China.
Department of Hematology, Suqian first people's Hospital, the Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu Province, 223800, China.
BMC Pulm Med. 2025 Aug 14;25(1):389. doi: 10.1186/s12890-025-03847-y.
Severe pneumonia is a lung parenchymal inflammation that can lead to multi-organ failure and death. Prostaglandin E1 (PGE1) is an autoreactive substance with extensive physiologic and pharmacologic properties. This study aims to investigate the ameliorative effect and potential mechanism of PGE1 in mice with severe pneumonia.
Mouse models of severe pneumonia were established by lipopolysaccharide (LPS), and the mice were administrated PGE1 to observe the effects of PGE1 on the pathological injury of lung tissues, wet-to-dry weight (W/D) ratio of lung tissues, levels of inflammatory factors in broncho-alveolar lavage fluid (BALF) and lung tissues, the number of white blood counts (WBCs) and polymorphonuclear neutrophils (PMNs) in BALF, blood gas indexes, and Th17/Treg balance. The critical signaling pathways of PGE1 involved in severe pneumonia were obtained by transcriptome sequencing (RNA-seq), and the regulatory role of PGE1 in alleviating severe pneumonia was observed by the JAK inhibitor AG490.
PGE1 can alleviate lung histopathological injury in mice with severe pneumonia, decrease W/D ratio, attenuate interleukin- 1β (IL-1β), interleukin- 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels, increase interleukin- 10 (IL-10) levels in mouse BALF and lung tissues, and reduce the number of WBCs and PMNs; it can increase the arterial blood partial pressure of oxygen (PaO) and decrease the arterial blood partial pressure of carbon dioxide (PaCO), and up-regulate the proportion of Treg cells, decrease RORγt expression, and increase Foxp3 expression. Differential gene expression analysis and enrichment analyses showed that the enrichment of JAK-STAT pathway was decreased in the LPS + PGE1 group compared to the LPS group. Joint use of PGE1 and AG490 can reduce p-JAK2 and p-STAT3 protein expression and synergistically improve the pathological damage phenotype in mice with severe pneumonia.
PGE1 can alleviate lung histopathological injury and reduce the degree of pulmonary edema in mice with severe pneumonia, and the mechanism might be realized by preventing PMN aggregation and activation in the lungs, reducing the release of inflammatory mediators, improving pulmonary ventilation, and regulating immune homeostasis. Moreover, by using transcriptome analysis and animal experiments, this study found that PGE1 participates in severe pneumonia by regulating JAK-STAT pathway.
重症肺炎是一种可导致多器官功能衰竭和死亡的肺实质炎症。前列腺素E1（PGE1）是一种具有广泛生理和药理特性的自身活性物质。本研究旨在探讨PGE1对重症肺炎小鼠的改善作用及其潜在机制。
通过脂多糖（LPS）建立重症肺炎小鼠模型，并给予小鼠PGE1，观察PGE1对肺组织病理损伤、肺组织湿干重（W/D）比、支气管肺泡灌洗液（BALF）和肺组织中炎症因子水平、BALF中白细胞计数（WBC）和多形核中性粒细胞（PMN）数量、血气指标以及Th17/Treg平衡的影响。通过转录组测序（RNA-seq）获得PGE1在重症肺炎中涉及的关键信号通路，并通过JAK抑制剂AG490观察PGE1在减轻重症肺炎中的调节作用。
PGE1可减轻重症肺炎小鼠的肺组织病理损伤，降低W/D比，减轻白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平，提高小鼠BALF和肺组织中白细胞介素-10（IL-10）水平，并减少WBC和PMN数量；可提高动脉血氧分压（PaO），降低动脉血二氧化碳分压（PaCO），上调Treg细胞比例，降低RORγt表达，增加Foxp3表达。差异基因表达分析和富集分析表明，与LPS组相比，LPS + PGE1组中JAK-STAT通路的富集程度降低。PGE1与AG490联合使用可降低p-JAK2和p-STAT3蛋白表达，并协同改善重症肺炎小鼠的病理损伤表型。
PGE1可减轻重症肺炎小鼠的肺组织病理损伤，降低肺水肿程度，其机制可能是通过防止肺内PMN聚集和激活、减少炎症介质释放、改善肺通气以及调节免疫稳态来实现。此外，通过转录组分析和动物实验，本研究发现PGE1通过调节JAK-STAT通路参与重症肺炎的发生发展。
