Protective effects of recombinant human brain natriuretic peptide against LPS-Induced acute lung injury in dogs

Abstract

Acute lung injury (ALI) is a common component of systemic inflammatory disease without more effective treatments. However, recent studies have demonstrated that the recombinant human brain natriuretic peptide (rhBNP) has anti-inflammatory effects. Therefore, we found that rhBNP could prevent lipopolysaccharide (LPS)-induced acute lung injury in a dog model. Dogs were injected with LPS and subjected to continuous intravenous infusion (CIV) of saline solution or rhBNP. We detected the protective effects of rhBNP by histological examination and determination of serum cytokine levels and lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) activity. Histological examination indicated marked inflammation, edema and hemorrhage in lung tissue taken 12h after rhBNP treatment compared with tissue from dogs which received saline treatment after LPS injection. LPS injection induced cytokine (IL-6 and TNF-α) secretion and lung MPO and MDA activities, which were also attenuated by rhBNP treatment. Inductions of IL-6 and TNF-α were significantly attenuated in the L-rhBNP and the H-rhBNP groups. The ratios of the L-rhBNP group and H-rhBNP group were lower than that in the lung injury group. Furthermore, MPO and MDA activities were significantly lower in the H-rhBNP group compared to those in the LI group. Our data indicate that rhBNP treatment may exert protective effects and may be associated with adjusting endogenous antioxidant enzymes. Thus, rhBNP may be considered as a therapeutic agent for various clinical conditions involving lung injury by sepsis.