Dexmedetomidine alleviates pulmonary ischemia-reperfusion injury through modulating the miR-21-5p/Nr4a1 signaling pathway

  • Wei Dong Department of Anesthesiology, The First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong Province, 515041, China https://orcid.org/0000-0002-0524-5379
  • Hongxia Yang Department of Sector 2 of Hepatic and Gallbladder Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong Province, 515041, China https://orcid.org/0000-0001-7461-4943
  • Minghua Cheng Department of Anesthesiology, The First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong Province, 515041, China https://orcid.org/0000-0002-4037-466X
  • Xin Zhang Department of Molecular Biology Laboratory, The First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong Province, 515041, China https://orcid.org/0000-0002-2402-8556
  • Jingjing Yin Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong Province, 515041, China https://orcid.org/0000-0002-6120-220X
  • Zhaodong Zeng Department of Anesthesiology, The First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong Province, 515041, China https://orcid.org/0000-0001-8831-9355
  • Guang Huang Department of paediatrics, The First Affiliated Hospital of Shantou University Medical College, Shantou City, Guangdong Province, 515041, China
DOI: https://doi.org/10.18388/abp.2020_5374

Abstract

This study aims to investigate the protection of dexmedetomidine (Dex) against pulmonary ischemia-reperfusion injury (PIRI) in the mouse model and reveal the mechanism in hypoxia reoxygenation (H/R)-induced mouse pulmonary vascular endothelial cells (MPVECs). The lung wet-to-dry weight ratio, histopathological features, and malondialdehyde (MDA) concentrations were measured. The H/R-induced MPVECs were exposed to Dex, and the cell viability, cell apoptosis and protein expressions were assessed by the Cell Counting Kit-8 (CCK8) assay, flow cytometry and western blot, respectively. In addition, the regulatory relationship between miR-21-5p and orphan nuclear receptor 4A1 (Nr4a1) was revealed by several assays, including the dual-luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. We found that the Dex treatment significantly alleviated pulmonary injury and decreased the level of MDA and wet/dry weight ratio in PIRI mice. Dex treatment also increased cell viability, reduced apoptotic ratio and downregulated expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 in H/R induced MPVECs. Furthermore, the expression of miR-21-5p was upregulated, while Nr4a1 was downregulated by Dex in a concentration-dependent manner in H/R induced MPVECs. Moreover, Nr4a1 was verified as a target of miR-497-5p. Overexpression of Nr4a1 could reverse the protective effects of Dex on alleviating H/R-induced injury in MPVECs. Taken together, Dex treatment attenuated ischemia-reperfusion induced pulmonary injury through modulating the miR-21-5p/Nr4a1 signaling pathway.

Published
2020-12-17
Issue
Vol. 67 No. 4 (2020)
Section
Articles

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