Dexmedetomidine relieves LPS-induced acute lung injury by boosting HIF-1a/ACOD1 driven anti-inflammatory macrophage polarization.

IF 4.5 3区 医学 Q1 GENETICS & HEREDITY
Ning Zhang, Tangbing Chen, Yintao Chang, Mingzhi Cao, Huan Wang, Chengli Wu, Hong Jiang
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引用次数: 0

Abstract

Acute lung injury (ALI) is a common and life-threatening lung disease. This study investigated the mechanism by which dexmedetomidine (Dex) alleviates lipopolysaccharide (LPS)-induced ALI, focusing on its regulation of macrophage autophagy and polarization. Initially, a mouse model of LPS-induced ALI was pretreated with Dex. Pulmonary function, histopathological changes, apoptosis, macrophage numbers in bronchoalveolar lavage fluid (BALF), M1/M2 macrophage ratios, iNOS/Arg-1/LC3/P62 fluorescence intensity, and autophagy flux were assessed. Subsequently, RAW264.7 macrophages were treated with LPS and Dex, transfected with si-ACOD1 or si-HIF-1α, and co-cultured with mouse pulmonary microvessel endothelial cells (MPMVECs). The results showed that Dex relieved autophagy flux blockage and promoted autophagy in ALI mice. LPS promoted ACOD1 and HIF-1α levels, and Dex further enhanced their levels to boost macrophage autophagy and M2 polarization. ACOD1 was transcriptionally regulated by HIF-1α. Collectively, Dex mitigated LPS-induced MPMVEC injury and ALI by enhancing HIF-1α-mediated ACOD1 transcription, thus promoting macrophage autophagy and M2 polarization.

右美托咪定通过增强HIF-1a/ACOD1驱动的抗炎巨噬细胞极化来缓解lps诱导的急性肺损伤。
急性肺损伤(ALI)是一种常见的危及生命的肺部疾病。本研究探讨右美托咪定(Dex)缓解脂多糖(LPS)诱导的ALI的机制,重点研究右美托咪定对巨噬细胞自噬和极化的调节作用。首先,用Dex预处理lps诱导的ALI小鼠模型。观察肺功能、组织病理学改变、细胞凋亡、支气管肺泡灌洗液(BALF)中巨噬细胞数量、M1/M2巨噬细胞比率、iNOS/Arg-1/LC3/P62荧光强度和自噬通量。随后,用LPS和Dex处理RAW264.7巨噬细胞,转染si-ACOD1或si-HIF-1α,与小鼠肺微血管内皮细胞(MPMVECs)共培养。结果表明,右美托咪唑能缓解ALI小鼠自噬通量阻塞,促进自噬。LPS提高ACOD1和HIF-1α水平,Dex进一步提高ACOD1和HIF-1α水平,促进巨噬细胞自噬和M2极化。ACOD1受HIF-1α的转录调控。Dex通过增强hif -1α-介导的ACOD1转录,从而促进巨噬细胞自噬和M2极化,从而减轻lps诱导的MPMVEC损伤和ALI。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes and immunity
Genes and immunity 医学-免疫学
CiteScore
8.90
自引率
4.00%
发文量
28
审稿时长
6-12 weeks
期刊介绍: Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.
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