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脓毒症诱导的急性肺损伤的潜在机制及候选药物

Potential mechanism and drug candidates for sepsis-induced acute lung injury.

作者信息

Xu Chenyuan, Guo Zhengqiang, Zhao Chuncheng, Zhang Xufeng, Wang Zheng

机构信息

Department of Thoracic Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.

出版信息

Exp Ther Med. 2018 Jun;15(6):4689-4696. doi: 10.3892/etm.2018.6001. Epub 2018 Mar 28.

DOI:10.3892/etm.2018.6001
PMID:29805488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5952104/
Abstract

The present study aimed to explore the mechanisms underlying sepsis-induced acute lung injury (ALI) and identify more effective therapeutic strategies to treat it. The gene expression data set GSE10474 was downloaded and assessed to identify differentially expressed genes (DEGs). Principal component analysis, functional enrichment analysis and differential co-expression analysis of DEGs were performed. Furthermore, potential target drugs for key DEGs were assessed. A total of 209 DEGs, including 107 upregulated and 102 downregulated genes were screened. A number of DEGs, including zinc finger and BTB domain containing 17 (), heat shock protein 90 kDa β, member 1 () and major histocompatibility complex, class II, DR α were identified. Furthermore, gene ontology terms including antigen processing and presentation, glycerophospholipid metabolism, transcriptional misregulation in cancer, thyroid hormone synthesis and pathways associated with diseases, such as asthma were identified. In addition, a differential co-expression network containing ubiquitin-conjugating enzyme E2 D4, putative and tubulin, γ complex associated protein 3 was constructed. Furthermore, a number of gene-drug interactions, including between and adenosine-5'-diphosphate and radicicol, were identified. Therefore, DEGs, including and , may be important in the pathogenesis of sepsis-induced ALI. Furthermore, drugs including adenosine-5'-diphosphate may be novel drug candidates to treat patients with ALI.

摘要

本研究旨在探讨脓毒症诱导的急性肺损伤(ALI)的潜在机制,并确定更有效的治疗策略。下载并评估基因表达数据集GSE10474以鉴定差异表达基因(DEG)。对DEG进行主成分分析、功能富集分析和差异共表达分析。此外,评估关键DEG的潜在靶标药物。共筛选出209个DEG,包括107个上调基因和102个下调基因。鉴定出一些DEG,包括含锌指和BTB结构域的17()、热休克蛋白90 kDaβ成员1()和主要组织相容性复合体II类DRα。此外,还鉴定出基因本体术语,包括抗原加工和呈递、甘油磷脂代谢、癌症中的转录失调、甲状腺激素合成以及与疾病相关的途径,如哮喘。此外,构建了一个包含泛素结合酶E2 D4、假定的和微管蛋白γ复合体相关蛋白3的差异共表达网络。此外,还鉴定出一些基因-药物相互作用,包括和5'-二磷酸腺苷与雷帕霉素之间的相互作用。因此,包括和在内的DEG可能在脓毒症诱导的ALI发病机制中起重要作用。此外,包括5'-二磷酸腺苷在内的药物可能是治疗ALI患者的新型候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/a7ad3abfdde5/etm-15-06-4689-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/9aa2b5a3bcd8/etm-15-06-4689-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/5b2b3fb412a3/etm-15-06-4689-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/92184bf26a45/etm-15-06-4689-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/88340b68cd3d/etm-15-06-4689-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/a7ad3abfdde5/etm-15-06-4689-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/9aa2b5a3bcd8/etm-15-06-4689-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/5b2b3fb412a3/etm-15-06-4689-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/92184bf26a45/etm-15-06-4689-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/88340b68cd3d/etm-15-06-4689-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d48/5952104/a7ad3abfdde5/etm-15-06-4689-g04.jpg

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