Mechanism of protective effect of sodium nitroprusside against endotoxin- induced acute lung injury in rats

Objective To investigate the effect of sodium nitroprusside (SNP) , an exogenous NO donor, on expression of hemeoxygenase-1 (HO-1) and inducible NO synthase (iNOS) in the lung tissue in a rat model of lpopolysaccharide (LPS)-induced acute lung injury and the underlying mechanism.Methods Thirty-two Wistar rats of either sex weighing 190-210 g were randomly divided into 4 groups ( n = 8 each) : Ⅰ sham operation (S) ;Ⅱ LPS;Ⅲ hemin + LPS and Ⅳ SNP + LPS. The animals were anesthetized with intraperitoneal (IP) 7% chloralhydrate 5 ml·kg-1. LPS 750 μg·kg-1 in 300 μl was instilled into the lungs via trachea in group Ⅱ . In group Ⅲ hemin (a HO-1 inducer) 40 μmol·kg-1 was injected IP 12 h before LPS. In group Ⅳ SNP 25 μg·kg-1 + LPS 750 μg·kg-1 in 300 μl was instilled into the lungs via trachea. In group S normal saline 300 μl was instilled via trachea instead of LPS. The animals were killed by (1) exsanguination from carotid artery 8h (2) after LPS instillation and lungs were removed for broncho-alveolar lavage (BAL) and detennination of protein concentration in BALF and the expression of HO-1 and iNOS protein in the lung tissue by immune-histochemical technique and HPIAS-2000 image analysis system and MDA content in lung tissue and (3) light microscopic examination (4) wet/ dry lung weight ratio.Results The 4 groups were comparable with respect to body weight and sex (M/F ratio) . The expression of iNOS and HO-1 in lung tissue was significantly higher in LPS group than in S group ( P 0.01) but the increase in iNOS expression was attenuated while the increase in HO-1 expression accentuated by HM pretreatment (group Ⅲ) and SNP administration (group Ⅳ). The W/D ratio, protein concentration in BALF and MDA content in lung tissue were all significantly increased by LPS in group Ⅱ as compared to S group and the increases were all attenuated by HM pretreatment (group Ⅱ) and SNP intratracheal instillation (group Ⅳ) . Microscopic examination showed that the histologic damage induced by LPS was mild in group HM and SNP compared with group LPS. Conclusion SNP ameliorates LPS-induced acute lung injury through induction of HO-1 which inhibits iNOS/NO.