Recombinant human brain natriuretic peptide ameliorates trauma-induced acute lung injury via inhibiting JAK/STAT signaling pathway in rats

BACKGROUND: JAK/STAT signal pathway plays an important role in the inflammation process of acute lung injury (ALI). This study aimed to investigate the correlation between recombinant human brain natriuretic peptide (rhBNP) and the JAK/STAT signaling pathway and to explore the protective mechanism of rhBNP against trauma-induced ALI. METHODS: The arterial partial pressure in oxygen, lung wet-dry weight ratios, protein content in bronchoalveolar lavage fluid, the histopathologic of the lung, as well as the protein expressions of STAT1, JAK2, and STAT3 were detected. RESULTS: Sprague-Dawley rats were randomly divided into five groups: a control group, a sham-operated group, an ALI group, an ALI + rhBNP group, and an ALI + AG490 group. At 4 hours, 12 hours, 1 day, 3 days, and 7 days after injury, injured lung specimens were harvested. rhBNP pretreatment significantly ameliorated hypoxemia and histopathologic changes and alleviated pulmonary edema in trauma-induced ALI rats. rhBNP pretreatment reduced the phosphorylated protein and total protein level of STAT1. Similarly to JAK-specific inhibitor AG490, rhBNP was shown to significantly inhibit the phosphorylation of JAK2 and STAT3 in rats with trauma-induced ALI. CONCLUSION: Our experimental findings indicated that rhBNP can protect rats against trauma-induced ALI and that its underlying mechanism may be related to the inhibition of JAK/STAT signaling pathway activation. (J Trauma Acute Care Surg. 2015; 78: 980-987. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.)