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

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.