Role of heme oxygenase-1/carbon monoxide in lung injury induced by hepatic ischemia-reperfusion in the rats with hyperdynamic circulation

Abstract

Objective To explore the protect role of heme oxygenase-1 (HO-1) in acote lung injury (ALl) induced by hepatic ischemia-repeffusion in rats with hyperdynamic circulation and its relation with carbon monoxide (CO). Methods Thirty-two male SD rats were randomly divided into four groups(n = 8) : sham operation group(S), hyperdynamic circulation group (HC) injected with llpopolysaccharide(10 μg/100 g)subcutaneously every two days for three weeks in prehepatic portal vein ligation (PVL) rats, hepatic ischemia-reperfusion group (HIR) operated by clamping chepatic hilum of HC rats for twenty minutes and reperfusion for 1 hour, Hernin group received heroin (inducer of HO-1) 50 mg/kg by intraperitoneal injection one hour before hepatic ischemia-reperfusion of HC rats. The rats were injected with Evans blue (30 mg/kg)then sacrificed with their longs taken out to determine the lung water ratio (W/ D), Evans blue content to calculate lung microvascular permeability. COHb% in arterial blood , as well as lung tissue myeloperoxidase (MPO), melonyldialdehyde (MDA), superoxide dismutase (SOD)activity. and HOd enzymatic activity were detected. Results Compared with S group and HC group, the lung water ratio (W/D), Evans blue content, MDA content and MPO content were significantly higher while SOD activity was significantly lower in HIR group and Heroin group (P <0.01). Compared with HIR group, Evans blue content, MDA content and MPO content were lower in Heroin group (P <0.05). Compared with S group and HC group, COHb% and HO-1 activity were higher in HIR group and Heroin group (P <0.01). Compared with HIR groop, COHb% and HO-1 activity in Heroin group was higher (P < 0. 05). Differience of portal hypertension among groups were significance (P < 0.01). Conelusion The increase of CO generation participates in the lung tissue protection during hepatic ischemia-reperfusion in rats with hyperdynamic circulation and this event is related to HO activity increase. Hemin up-regulates the HO-1/CO system in the lung tissues during I/R, which may be the endogenous compensatory response against the injury. Key words: Hyperdynamics circulation; HO-1/CO ; Lung injury ; Hepatic isehemia-reperfusion; Rats