Midkine exacerbates inflammation, apoptosis and oxidative stress in heart of septic mice

Abstract

Abstract Aim: Midkine inhibition ameliorates sepsis induced lung injury. This research was to explore the influences of midkine on the sepsis-associated heart damage and the mechanisms. Methods: Sepsis models were established via lipopolysaccharide (LPS) induction in mice in vivo, and in HL-1 cells in vitro. Results: The expressed levels of midkine raised in the heart of mice and HL-1 cells by treating with LPS. The cardiac dysfunction of septic mice was deteriorated by midkine overexpression and was improved by midkine knockdown. The increases of inflammatory factors in the heart of mice induced by LPS were further enhanced by midkine overexpression and were attenuated by midkine knockdown. The increase of myocardial apoptosis in septic mice was worsened after midkine overexpression and was alleviated after midkine downregulation. The oxidative stress increase in the heart of septic mice was exacerbated by overexpression of midkine and was attenuated by downregulation of midkine. Conclusions: These results indicated that midkine exacerbated cardiac dysfunction via enhanced inflammation, apoptosis and oxidative stress. Targeting of midkine could improve cardiac dysfunction via attenuation of inflammation, apoptosis and oxidative stress.