Authors

Yanxiao Long, Xuqing Ni, Beiping Chen, Nengli Yang, Tianqi Zhu#

Departments

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Abstract

Objective: To investigate the role of DAPK1 in the process of acute lung injury by regulating the p38-mTOR signalling pathway. 

Methods: Forty clean C57BL/6 mice were randomly divided into a normal control group and lipopolysaccharide (LPS) treatment 2, 4, 12, 24 h groups, with eight mice in each group. The acute lung injury (ALI) model was established by intraabdominal injection of LPS (10mg/kg) into the LPS treatment group, and normal saline of equal volume was given to the control group. The changes of DAPK1 in the lung tissue of ALI mice and the DAPK1 mRNA and protein in the lung tissue of ALI mice were detected by an immunohistochemical method. Macrophage cells were stimulated by LPS at concentrations of 100, 200, 500, 1000 ng/ml, respectively, and the blank control group was set up to observe the effect of different concentrations of LPS on the expression of DAPK1. The expression of p38 and mTOR proteins were detected by Western imprinting. 

Results: The number of DAPK1 cells in the lung tissue of the treated group was significantly higher than that of the control group at each time point after LPS treatment, and the expression of DAPK1 protein in the lung tissue of the treated group was significantly higher than that of the normal control group (P<0.05). The expression of DAPK1 mRNA in the lung tissue of the treated group was significantly higher than that of the normal control group at each time point (P<0.05). The expression of DAPK1 mRNA and protein in macrophages stimulated by different concentrations of LPS for 24 hours was significantly higher than that in the control group and increased gradually with the increase of concentration. The expression of p38 and mTOR proteins in the normal control group was less than that in the normal control group and increased significantly under the stimulation of LPS. After DAPK1 shRNA silencing DAPK1, the expression of p38 and mTOR proteins was significantly lower than that in the LPS group alone, suggesting that autophagy is closely related to the p38-mTOR signalling pathway. 

Conclusion: The expression of DAPK1 in lung tissue of mice with acute lung injury is significantly increased, which may inhibit macrophage participation in the pathogenesis of acute lung injury by regulating the p38-mTOR signalling pathway.

Keywords

DAPK1, p38-mTOR signalling pathway, acute lung injury.

DOI:

10.19193/0393-6384_2020_3_209