[Total hepatic ischemia-reperfusion-induced lung injury in rats and protective effects of melatonin]

To explore total hepatic ischemia-reperfusion(I/R)-induced lung injury in rats,its related mechanism and the protective effects of melatonin on lungs.

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.

(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 gradually. 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<0.05) and apoptotic index (r=0.62, P<0.05) in I/R group. (2)Melatonin treatment alleviated total hepatic I/R-induced lung injury. In melatonin group, the histological change was less severe compared with that in vehicle group; the MDA content and apoptotic index were lower, the SOD activity and p-ERK/ERK ratio were higher than those in vehicle group at the same time, but PCNA-positive index showed no difference.

Total hepatic I/R led to severe lung injury. The aggravation of lipid peroxidation, reduced capability of scavenging free radical and aggravation of apoptosis were important factors causing hepatic I/R induced lung injury. Melatonin had protective effect on lung injury induced by total hepatic I/R, which was mediated by anti-oxidation and anti-apoptosis, but the relationship between melatonin's protective effects and activation of ERK1/2 signal transduction pathway remained to be explored.