Total hepatic ischemia-reperfusion-induced lung injury in rats and protective effects of melatonin / 北京大学学报(医学版)

ABSTRACT

Objective:To explore total hepatic ischemia-reperfusion(I/R)-induced lung injury in rats,its related mechanism and the protective effects of melatonin on lungs.Methods: This study was divided into 2 parts.In the first part,72 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups I/R group(ischemia-reperfusion,n=36) and sham-operation group(n=36).Total hepatic I/R was produced by occlusion of hepatic helium for 30 minutes,and the occlusion was then released for reperfusion.The animals were killed at 5 minutes prior to ischemia and 0 h,0.5 h,1 h,3 h and 6 h after reperfusion in sham-operation group and I/R group(n=6 at each time point),and the lung tissue was taken.Through comparisons of these two groups,we observed the dynamic changes of lung tissue after total hepatic I/R.In the second part,12 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups melatonin group(n=6) and vehicle group(n=6).Melatonin(0.5%,10 mg/kg)or vehicle of the same volume was injected via femoral vein 15 min before ischemia and 10 min before reperfusion,the animals were killed at 1 h after reperfusion,and the lung tissue was taken.Through comparisons of these two groups,we observed the effects of melatonin.Results:(1)Total hepatic I/R led to severe histological injury in lungs.Compared with those in sham-operation group,the MDA content and apoptotic index were increased,the SOD activity was decreased,the p-ERK/ERK ratio and PCNA-positive index were decreased respectively 0 h and 0.5 h after reperfusion,and then were increased gra-dually.Histological examination revealed that the alveolar architecture was destroyed with interstitial thickening and neutrophil infiltration in I/R group.Correlate analysis revealed that p-ERK/ERK ratio showed a positive correlation with PCNA-positive index(r=0.56,P