Increased inflammation is the key mechanism that mediates sepsis induced cardiac injury. Resolvin D1 (RvD1), a bioactive lipid mediator synthesized from docosahexaenoic acid, can attenuate the severity of many inflammation-related diseases through anti-inflammatory and pro-resolving properties. However, the protective role of RvD1 in sepsis induced cardiac injury remains unclear. Mice were randomly divided into three groups: the control group, LPS group and RvD1 + LPS group. LPS (10 mg/kg, i.p.) was used to establish a sepsis-induced cardiac injury model. RvD1 (5 ug/kg, i.p.) was injected 30 min before LPS injection. RvD1 treatment significantly attenuated the deteriorated cardiac function and cardiac injury induced by LPS, as evidenced by the improved left ventricular ejection fraction, serum levels of cardiac injury markers and severity of cardiomyocyte apoptosis. In addition, RvD1 treatment significantly attenuated the infiltration of pro-inflammatory M1 macrophages and expression of inflammatory cytokines in the heart. Mechanistically, the attenuated activation of NK-κB and MAPK signaling mediated the anti-inflammatory and antiapoptotic effects of RvD1. In addition, LPS-induced infiltration of neutrophils and M1 macrophages in the spleen was significantly attenuated by the RvD1 treatment. Results of the present study suggest that RvD1 protects the heart against LPS-induced injuries by attenuating the local and systemic inflammatory response, highlighting the therapeutic effects of RvD1 in sepsis-induced cardiac injury.
Keywords: Sepsis; inflammation resolution; macrophage; specialized pro-resolving mediators; spleen.
© 2020 International Union of Biochemistry and Molecular Biology.