Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005 Hunan, China.
Department of Science and Education, The First Hospital of Changsha, Changsha, 410008 Hunan, China.
Biomed Res Int. 2022 Apr 13;2022:3330552. doi: 10.1155/2022/3330552. eCollection 2022.
Acute lung injury (ALI) is an acute hypoxic respiratory failure caused by diffuse inflammatory injury in alveolar epithelial cells during severe infection, trauma, and shock. Among them, trauma/hemorrhagic shock (T/HS) is the main type of indirect lung injury. Despite a great number of clinical studies, indirect factor trauma/hemorrhagic shock to the function and the mechanism in acute lung injury is not clear yet. Therefore, it is still necessary to carry on relevant analysis in order to thoroughly explore its molecular and cellular mechanisms and the pathway of disease function. In our research, we aimed to identify potential pathogenic genes and do modular analysis by downloading disease-related gene expression profile data. And our dataset is from the NCBI-GEO database. Then, we used the Clusterprofiler R package, GO function, and KEGG pathway enrichment analysis to analyze the core module genes. In addition, we also identified key transcription factors and noncoding RNAs. Based on the high degree of interaction of potential pathogenic genes and their involved functions and pathways, we identified 17 dysfunction modules. Among them, up to 9 modules significantly regulate the response to bacterial-derived molecules, and the response to lipopolysaccharide and other related functional pathways that mediate disease development. In addition, miR-290, miR-30c-5p, miR-195-5p, and miR-1-3p-based ncRNA and Jun, Atf1, and Atf3-based transcription factors have a total of 80 transcription drivers for functional modules. In summary, this study confirmed that miR-30c-5p activates lipopolysaccharide response pathway to promote the pathogenesis of ALI induced by hemorrhagic shock. This result can be an important direction for further research on related deepening diseases such as acute respiratory distress syndrome (ARDS). It further provides a piece of scientific medical evidence for revealing the pathogenic principle and cure difficulty of acute lung injury and also provides important guidance for the design of therapeutic strategies and drug development.
急性肺损伤（ALI）是一种由严重感染、创伤和休克期间肺泡上皮细胞弥漫性炎症损伤引起的急性低氧性呼吸衰竭。其中，创伤/失血性休克（T/HS）是间接性肺损伤的主要类型。尽管进行了大量的临床研究，但间接因素创伤/失血性休克对急性肺损伤的功能和机制仍不清楚。因此，仍有必要进行相关分析，以彻底探讨其分子和细胞机制以及疾病功能的途径。在我们的研究中，我们旨在通过下载疾病相关基因表达谱数据来识别潜在的致病基因并进行模块分析。我们的数据集来自 NCBI-GEO 数据库。然后，我们使用 Clusterprofiler R 包、GO 功能和 KEGG 途径富集分析来分析核心模块基因。此外，我们还鉴定了关键的转录因子和非编码 RNA。基于潜在致病基因及其涉及的功能和途径的高度相互作用，我们确定了 17 个功能失调模块。其中，多达 9 个模块显著调节对细菌来源分子的反应，以及对介导疾病发展的脂多糖和其他相关功能途径的反应。此外，基于 miR-290、miR-30c-5p、miR-195-5p 和 miR-1-3p 的 ncRNA 和基于 Jun、Atf1 和 Atf3 的转录因子总共对 80 个功能模块具有转录驱动作用。总之，这项研究证实，miR-30c-5p 激活脂多糖反应途径，促进失血性休克诱导的 ALI 的发病机制。这一结果可以为进一步研究相关深化疾病（如急性呼吸窘迫综合征（ARDS））提供重要方向。它进一步为揭示急性肺损伤的发病原理和治疗难度提供了科学的医学证据，也为治疗策略的设计和药物开发提供了重要指导。
