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右美托咪定对脂多糖诱导的急性肺损伤中 tsRNAs 表达谱的影响。

Effects of dexmedetomidine on the expression profile of tsRNAs in LPS-induced acute lung injury.

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang City, China.

出版信息

J Clin Lab Anal. 2022 Jan;36(1):e24115. doi: 10.1002/jcla.24115. Epub 2021 Nov 22.

Abstract

BACKGROUND

Acute lung injury (ALI) is characterized by impaired alveolar function and excessive inflammation, which is commonly seen in clinical anesthesia and intensive care units. tRNA-derived small RNA (tsRNA) is a non-coding RNA that can be used as a potential disease diagnostic biomarker. The connection between ALI and tsRNA remains unknown. We aimed to explore the possible regulatory functions and mechanisms of tsRNAs in ALI treated with DEX.

METHODS

Firstly, we established the ALI model by LPS injection and explored the effect of dexmedetomidine (DEX) treatment on lung damage. Then, the lung tissues were obtained from the LPS and LPS + DEX group for small RNA sequencing.

RESULTS

We proved that DEX could ameliorate pulmonary injury, and decreased inflammation, pulmonary edema, and ferroptosis (MDA down-regulation and GPX4 up-regulation) in ALI. Furthermore, in the tsRNA expression profile, the top 10 down-regulated tsRNAs were tsRNA-1018, tsRNA-3045b, tsRNA-5021a, tsRNA-1020, tsRNA-5002b, tsRNA-3045b, tsRNA-1026, tsRNA-5004a, tsRNA-5005b and tsRNA-1009, and the top 10 up-regulated tsRNAs were tsRNA-3025b, tsRNA-3025a, tsRNA-5016b, tsRNA-3042b, tsRNA-3029b, tsRNA-3028b, tsRNA-5006a, tsRNA-3027b, tsRNA-3027a, and tsRNA-5009b. The enrichment analysis of GO terms and KEGG pathways pointed that target genes of DE-tsRNAs were mainly enriched in regulation of transcription-associated GO terms, NF-kappa B signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. The RT-qPCR results of tsRNA-1020 and tsRNA-1018 were in accordance with small RNA sequencing data.

CONCLUSION

DEX affected the abnormal expression of tsRNAs in ALI. These aberrantly expressed tsRNAs and enriched physiological processes provide a scientific basis for the diagnosis and treatment of ALI.

摘要

背景

急性肺损伤(ALI)的特征是肺泡功能受损和过度炎症,这在临床麻醉和重症监护病房中很常见。tRNA 衍生的小 RNA(tsRNA)是一种非编码 RNA,可以作为潜在的疾病诊断生物标志物。ALI 与 tsRNA 之间的联系尚不清楚。我们旨在探讨 tsRNA 在 DEX 治疗 ALI 中的可能调节功能和机制。

方法

首先,我们通过 LPS 注射建立了 ALI 模型,并探讨了右美托咪定(DEX)治疗对肺损伤的影响。然后,从 LPS 和 LPS+DEX 组的肺组织中获得小 RNA 测序。

结果

我们证明 DEX 可以改善 ALI 中的肺损伤,并降低炎症、肺水肿和铁死亡(MDA 下调和 GPX4 上调)。此外,在 tsRNA 表达谱中,下调最多的前 10 个 tsRNA 是 tsRNA-1018、tsRNA-3045b、tsRNA-5021a、tsRNA-1020、tsRNA-5002b、tsRNA-3045b、tsRNA-1026、tsRNA-5004a、tsRNA-5005b 和 tsRNA-1009,上调最多的前 10 个 tsRNA 是 tsRNA-3025b、tsRNA-3025a、tsRNA-5016b、tsRNA-3042b、tsRNA-3029b、tsRNA-3028b、tsRNA-5006a、tsRNA-3027b、tsRNA-3027a 和 tsRNA-5009b。GO 术语和 KEGG 途径的富集分析表明,DE-tsRNA 的靶基因主要富集在转录相关的 GO 术语、NF-kappa B 信号通路、MAPK 信号通路和 PI3K-Akt 信号通路的调控。tsRNA-1020 和 tsRNA-1018 的 RT-qPCR 结果与小 RNA 测序数据一致。

结论

DEX 影响 ALI 中 tsRNA 的异常表达。这些异常表达的 tsRNA 和丰富的生理过程为 ALI 的诊断和治疗提供了科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eedc/8761442/b9d8149bea59/JCLA-36-e24115-g001.jpg

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