Zhang Shi, Chen Hanbing, Xie Jianfeng, Huang Lili
Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Department of Respiratory and Critical Care Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
Front Med (Lausanne). 2024 Nov 1;11:1501761. doi: 10.3389/fmed.2024.1501761. eCollection 2024.
Pneumonia is a common clinical condition primarily treated with antibiotics and organ support. Exploring the pathogenesis to identify therapeutic targets may aid in the adjunct treatment of pneumonia and improve survival rates.
Transcriptomic data from peripheral blood of 183 pneumonia patients were analyzed using Gene Set Variation Analysis (GSVA) and univariate Cox regression analysis to identify signaling pathways associated with pneumonia mortality. A pneumonia mouse model was established via airway injection of , and pathway-specific blockers were administered via tail vein infusion to assess whether the identified signaling pathways impact the mortality in pneumonia.
The combination of GSVA and Cox analysis revealed 17 signaling pathways significantly associated with 28-day mortality in pneumonia patients ( < 0.05). Notably, the RIG-I-like receptor signaling pathway exhibited the highest hazard ratio of 2.501 with a 95% confidence interval of [1.223-5.114]. Infusion of RIG012 via the tail vein effectively inhibited the RIG-I-like receptor signaling pathway, significantly ameliorated lung injury in pneumonia mice, reduced pulmonary inflammatory responses, and showed a trend toward improved survival rates.
RIG012 may represent a novel adjunctive therapeutic agent for pneumonia.
肺炎是一种常见的临床病症，主要通过抗生素和器官支持进行治疗。探索其发病机制以确定治疗靶点可能有助于肺炎的辅助治疗并提高生存率。
使用基因集变异分析（GSVA）和单变量Cox回归分析对183例肺炎患者外周血的转录组数据进行分析，以确定与肺炎死亡率相关的信号通路。通过气道注射建立肺炎小鼠模型，并通过尾静脉输注给予通路特异性阻滞剂，以评估所确定的信号通路是否影响肺炎的死亡率。
GSVA和Cox分析相结合显示，17条信号通路与肺炎患者的28天死亡率显著相关（<0.05）。值得注意的是，RIG-I样受体信号通路的风险比最高，为2.501，95%置信区间为[1.223 - 5.114]。通过尾静脉输注RIG012可有效抑制RIG-I样受体信号通路，显著改善肺炎小鼠的肺损伤，减轻肺部炎症反应，并显示出生存率提高的趋势。
RIG012可能是一种新型的肺炎辅助治疗药物。
