MiR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14.

Li Ding,Shenghui Yu,Xiang Gao,Liufang Sheng

doi:10.1007/s10863-020-09842-8

Abstract

To investigate the role of miR-128-3p and MAPK14 in the dexmedetomidine treatment of acute lung injury in septic mice. SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO2, PaCO2, MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to detect the targeting relationship of miR-128-3p and MAPK14, and qPCR and WB were used to detect the expression of miR-128-3p and MAPK14. Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased (all p < 0.05). Compared with the Model group, the contents of MDA, MPO, inflammatory factors in the DEX group and miR-128-3p mimic group were significantly decreased, and the content SOD was significantly increased, however, opposite results were occurred in oe-MAPK14 group (all p < 0.05). Compared with the DEX group, all the indicators in miR-128-3p mimic+DEX group showed significant improvement (all p < 0.05). Compared with the miR-128-3p mimic group, all the indicators were deteriorated in the miR-128-3p mimic+oe-MAPK14 group (all p < 0.05). The combination of DEX and oe-MAPK14 blocked the protective effect of dexmedetomidine on acute lung injury in septic mice. miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.

Highlights

To investigate the role of miR-128-3p and MAPK14 in the dexmedetomidine treatment of acute lung injury in septic mice
Mice were divided into 8 groups: Normal group, Model group, DEX group, miR-128-3p mimic group, oe-MAPK14 group, miR-128-3p mimic + oe-MAPK14 group, miR-128-3p mimic + DEX group, DEX + oe-MAPK14 group, with ten mice in each group
We evaluated the protective effect of dexmedetomidine on sepsis-induced lung injury and we found that after the injection of Dex, the expression of MAPK14 was down-regulated, and inflammatory response and oxidative stress damage were alleviated

Summary

Introduction

To investigate the role of miR-128-3p and MAPK14 in the dexmedetomidine treatment of acute lung injury in septic mice. Sepsis is the most common systemic clinical complication of severe trauma, burns and major surgery, which can deteriorate into multiple organ dysfunction syndrome, becoming the leading cause of death in these patients [1]. Sepsis is considered to be an organ failure syndrome caused by immune disorders in the case of severe infection [2]. Excessive inflammatory response induced by sepsis can lead to multiple organ damage and failure. Acute lung injury (ALI) is a common complication of sepsis as lung is sensitive to sepsis damage [3]. ALI is characterized by progressive hypoxemia, enhanced vascular permeability, edema, neutrophil infiltration and lung accumulation, which greatly increases patient morbidity and mortality [4]. The researches on the new targets for the treatments of sepsis are hotspot [5]

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