Li Man, Ren Xiaojing, Lu Futai, Pang Shenyue, Ding Ling, Wang Lei, Xie Shuhua, Geng Licheng, Xu Jiangang, Yang Tao
Department of Anesthesiology, Tianjin Union Medical Center, Tianjin, China.
Department of Anesthesiology, Tianjin Baodi Hospital, Tianjin, China.
Shock. 2025 Jan 1;63(1):141-154. doi: 10.1097/SHK.0000000000002478. Epub 2024 Sep 11.
Background: Acute respiratory distress syndrome (ARDS) is a serious pathological process with high mortality. Ferroptosis is pivotal in sepsis, whose regulatory mechanisms in sepsis-induced ARDS remains unknown. We aimed to determine key ferroptosis-related genes in septic ARDS and investigate therapeutic traditional Chinese medicine. Method: Sepsis-induced ARDS dataset obtained from Gene Expression Omnibus was analyzed to identify ferroptosis-related differentially expressed genes. Enrichment analysis and protein-protein interaction network construction were performed to identify hub genes. Immune cells infiltration was analyzed and competitive endogenous RNA network was constructed. The diagnostic value of hub genes in septic ARDS was analyzed and the occurrence of ferroptosis and the expression of hub genes were detected. Traditional Chinese medicine targeting hub genes was predicted via SymMap database and was verified. Results: Sixteen ferroptosis-related differentially expressed genes were obtained, among which the top four genes ( IL1B , TXN , MAPK3 , HSPB1 ) were selected as hub genes, which may be potential diagnostic markers of septic ARDS. Immunoassay showed that sepsis-induced ARDS and hub genes were closely related to immune cells. The competitive endogenous RNA network showed 26 microRNAs and 38 long noncoding RNA. Ferroptosis occurred and the expressions of IL1B , MAPK3 , and TXN were increased in septic ARDS mice and LPS-challenged human pulmonary alveolar epithelial cells. Sea buckthorn alleviated septic lung injury and affected hub genes expression. Conclusions: Ferroptosis-related genes of IL1B , MAPK 3, and TXN serve as potential diagnostic genes for sepsis-induced ARDS. Sea buckthorn may be therapeutic medication for ARDS. This study provides a new direction for septic ARDS treatment.
急性呼吸窘迫综合征（ARDS）是一种死亡率高的严重病理过程。铁死亡在脓毒症中起关键作用，其在脓毒症诱导的ARDS中的调节机制尚不清楚。我们旨在确定脓毒症相关性ARDS中与铁死亡相关的关键基因，并研究治疗性中药。方法：分析从基因表达综合数据库获得的脓毒症诱导的ARDS数据集，以鉴定与铁死亡相关的差异表达基因。进行富集分析和蛋白质-蛋白质相互作用网络构建以鉴定枢纽基因。分析免疫细胞浸润并构建竞争性内源性RNA网络。分析枢纽基因在脓毒症相关性ARDS中的诊断价值，并检测铁死亡的发生和枢纽基因的表达。通过SymMap数据库预测并验证靶向枢纽基因的中药。结果：获得了16个与铁死亡相关的差异表达基因，其中前四个基因（IL1B、TXN、MAPK3、HSPB1）被选为枢纽基因，它们可能是脓毒症相关性ARDS的潜在诊断标志物。免疫分析表明，脓毒症诱导的ARDS和枢纽基因与免疫细胞密切相关。竞争性内源性RNA网络显示有26个微小RNA和38个长链非编码RNA。在脓毒症相关性ARDS小鼠和脂多糖刺激的人肺泡上皮细胞中发生了铁死亡，且IL1B、MAPK3和TXN的表达增加。沙棘减轻了脓毒症肺损伤并影响枢纽基因表达。结论：IL1B、MAPK 3和TXN等与铁死亡相关的基因可作为脓毒症诱导的ARDS的潜在诊断基因。沙棘可能是ARDS的治疗药物。本研究为脓毒症相关性ARDS的治疗提供了新方向。
