| 58 | 0 | 222 |
| 下载次数 | 被引频次 | 阅读次数 |
目的：探索非编码RNA(ncRNA)，尤其是长链非编码RNA(lncRNA)在脓毒症病理进程中的调控作用，为脓毒症的早期诊断提供新型生物标志物，并寻找干预免疫失衡的潜在治疗靶点。方法：收集脓毒症患者和健康人群的外周血标本，通过ceRNA芯片技术，对脓毒症中lncRNA的特异性表达谱进行系统性分析，结合微小RNA(miRNA)和环状RNA(circRNA)的相互作用网络，研究lncRNA在脓毒症中的调控机制。结果：lncRNA在脓毒症中呈现显著差异表达，其中包括差异表达的248个上调和26个下调lncRNA。结合GO富集分析及KEGG通路分类分析，结果显示lncRNA可能通过ceRNA机制参与炎症风暴和免疫抑制的调控，部分lncRNA与脓毒症的免疫失衡密切相关，具有作为生物标志物或治疗靶点的潜力。结论：lnc RNA在脓毒症的病理进程中发挥关键作用，其特异性表达谱为脓毒症的早期诊断提供了新的候选生物标志物，同时为干预免疫失衡的治疗策略提供了潜在靶点。
Abstract：Objective: To explore the regulatory role of non-coding RNAs(ncRNAs), particularly long non-coding RNAs(lncRNAs), in the pathological progression of sepsis, to identify novel biomarkers for early diagnosis, and to discover potential therapeutic targets for intervening in immune imbalance. Methods: Peripheral blood samples from patients with sepsis and healthy individuals were collected. We systematically analyzed the specific expression profiles of lncRNAs in sepsis through ceRNA microarray technology. We investigated the regulatory mechanisms of lncRNAs in sepsis by integrating the interaction networks of microRNAs( miRNAs) and circular RNAs( circRNAs). Results: The study revealed that lncRNAs exhibited significant differential expression in sepsis, including 248 up-regulated and 26 down-regulated lncRNAs with differential expression. Combining GO enrichment analysis and KEGG pathway classification analysis, the results indicated that lncRNAs might participate in the regulation of inflammatory storms and immunosuppression through the ceRNA mechanism. Certain lncRNAs were closely associated with immune imbalance in sepsis, demonstrating potential as biomarkers or therapeutic targets. Conclusion: lncRNAs play a critical role in the pathological progression of sepsis. Their specific expression profiles provide novel candidate biomarkers for early diagnosis of sepsis and offer potential targets for therapeutic strategies aimed at modulating immune dysregulation.
[1] ARINA P,HOFMAENNER D A,SINGER M. Definition and epidemiology of sepsis[J]. Semin Respir Crit Care Med,2024,45(4):461-468.
[2] DELLINGER R P,RHODES A,EVANS L,et al. Surviving sepsis campaign[J]. Crit Care Med,2023,51(4):431-444.
[3] SCHLAPBACH L J,WATSON R S,SORCE L R,et al. International consensus criteria for pediatric sepsis and septic shock[J]. JAMA,2024,331(8):665-674.
[4]常心怡，韩艺.巨噬细胞极化在脓毒症免疫及器官功能障碍中的作用[J].南京医科大学学报（自然科学版），2024,44(7):985-991.
[5] VINKEL J,RIB L,BUIL A,et al. Key pathways and genes that are altered during treatment with hyperbaric oxygen in patients with sepsis due to necro tizing soft tissue infection(HBOmic study)[J]. Eur J Med Res,2023,28(1):507.
[6] PANNI S,LOVERING R C,PORRAS P,et al. Non-coding RNA regulatory networks[J]. Biochim Biophys Acta Gene Regul Mech,2020,1863(6):194417.
[7] AHMAD BHAT A,RIADI Y,AFZAL M,et al. Exploring ncRNA-mediated pathways in sepsis-induced pyroptosis[J].Pathol Res Pract,2024,256:155224.
[8] FORMOSA A,TURGEON P,DOS SANTOS C C. Role of miRNA dysregulation in sepsis[J]. Mol Med,2022,28(1):99.
[9] BRIDGES M C,DAULAGALA A C,KOURTIDIS A. LNCcation:lncRNA localization and function[J]. J Cell Biol,2021,220(2):e202009045.
[10] HERMAN A B,TSITSIPATIS D,GOROSPE M. Integrated lncRNA function upon genomic and epigenomic regulation[J]. Mol Cell,2022,82(12):2252-2266.
[11] GRAMMATIKAKIS I ,LAL A. Significance of lncRNA abundance to function[J]. Mamm Genome,2022,33(2):271-280.
[12] MADHUGIRI R,NGUYEN H V,SLANINA H,et al. Alpha-and betacoronavirus Cis-acting RNA elements[J].Curr Opin Microbiol,2024,79:102483.
[13] LIU W,GENG F,YU L. Long non-coding RNA MALAT1/microRNA 125a axis presents excellent value in discriminating sepsis patients and exhibits positive association with general disease severity,organ injury,inflammation level,and mortality in sepsis patients[J]. J Clin Lab Anal,2020,34(6):e23222.
[14] H魻PFLER M,ABSMEIER E,PEAK-CHEW S Y,et al.Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation[J]. Mol Cell,2023,83(13):2290-2302.
[15] SHETTY A ,VENKATESH T ,KABBEKODU S P ,et al.LncRNA-miRNA-mRNA regulatory axes in endometrial cancer:a comprehensive overview[J]. Arch Gynecol Obstet,2022,306(5):1431-1447.
[16] ABE M,SHIGA H,TATSUMI H,et al. Results of the 2018Japan society for blood purification in critical care survey:current status and outcomes[J]. Ren Replace Ther,2022,8(1):58.
[17] LI S L,LI X,JIANG S S,et al. Identification of sepsis-associated mitochondrial genes through RNA and single-cell sequencing approaches[J]. BMC Med Genomics,2024,17(1):120.
[18] WANG R,ZHAO J L,WEI Q,et al. Potential of circulating lncRNA CASC2 as a biomarker in reflecting the inflammatory cytokines,multi-organ dysfunc tion,disease severity,and mortality in sepsis patients[J]. J Clin Lab Anal ,2022,36(8):e24569.
[19]钱镭元，修光辉，孙洁，等. lncRNA-miRNA-mRNA轴在脓毒症炎症免疫机制中的研究进展[J].华中科技大学学报（医学版），2023,52(1):117-122.
[20] XUE R,YIU W H,CHAN K W,et al. Long non-coding RNA NEAT1,NOD-like receptor family protein 3 inflammasome,and acute kidney injury[J]. J Am Soc Nephrol,2024,35(8):998-1015.
[21] LI J,WU X,LI C,et al. Identification and Validation of Immune-Related Biomarker Gene and Construction of ceRNA Networks in Septic Cardiomyopathy[J]. Front Cell Infect Microbiol,2022,12:912492.
[22] KELLY M J,BREATHNACH C,TRACEY K J,et al. Manipulation of the inflammatory reflex as a therapeutic strategy[J]. Cell Rep Med,2022,3(7):100696.
基本信息:
DOI：10.19767/j.cnki.32-1412.2025.05.002
中图分类号:R459.7
引用信息:
[1]关宇雯,梁桂文,黄中伟,等.脓毒症相关长链非编码RNA筛选及竞争性内源RNA网络构建[J].交通医学,2025,39(05):449-457.DOI:10.19767/j.cnki.32-1412.2025.05.002.