Pulmonary midkine inhibition ameliorates sepsis induced lung injury

Abstract Background Midkine is a multi-functional molecule participating in various key pathological process. We aimed to evaluate the change of midkine sepsis and its association with angiotensin-converting enzyme (ACE) system, as well mechanism by which induced lung injury. Methods The peripheral blood sample septic patients on admission was obtained measured for midkine, ACE angiotensin II. Cecal ligation puncture (CLP) mouse model used, adeno-associated virus (AAV) stilled trans-trachea regional targeting expression, comparing severity Furthermore, we studied vitro activates system using inhibitors candidate receptors effects vascular endothelial cells. Results Plasma significantly elevated sepsis, closely associated system. Both circulating increased CLP mouse, related severe Regional interfering expression tissue AAV could alleviate acute injury model. In study elucidated that Notch 2 participated activation II release, triggered reactive oxygen species production. Conclusions inhibition ameliorates injury, might via ACE/Ang pathway participation stimulation ACE. Trial registration Clinicaltrials.gov NCT02605681. Registered 12 November 2015