title: Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.
abstract: Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI.
authors: Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military District, Shenyang, China.
authors: Zhi
authors: Z
authors: Song
authors: Centralab, School of Stomatology, The Shenyang Medical College, Shenyang, China.
authors: Xiu
authors: X
authors: Zhao
authors: Pulmonary, Critical Care, Sleep & Allergy Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Martin
authors: M
authors: Liu
authors: Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military District, Shenyang, China.
authors: Hongxu
authors: H
authors: Jin
authors: Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military District, Shenyang, China.
authors: Ling
authors: L
authors: Wang
authors: Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military District, Shenyang, China.
authors: Mingxiao
authors: M
authors: Hou
authors: Department of Emergency and Critical Care Medicine, The General Hospital of Shenyang Military District, Shenyang, China.
authors: Yan
authors: Y
authors: Gao
mesh_terms: D055371:Acute Lung Injury / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D059748:Proteolysis; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D011994:Recombinant Proteins; D020097:Natriuretic Peptide, Brain; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: NF-κB; acute lung injury; antioxidative enzymes; brain natriuretic peptide; trauma/haemorrhagic shock