Research Of Amiloride And Its Protective Role In Ischemia-reperfusion Injury In Rat Lung

Purpose To study the mechanism of lung ischemia- reperfusion injury and the protective effects of Amiloride on lung ischemia- reperfusion injury.Methods Fifty-four healthy male Wistar rats were randomly divided into three groups: surgical control group (C group), ischemia-reperfusion group (IR group),and amiloride- pretreated group (A group). At each of three time spots(45 min ischemia,60 min and 120 min reperfusion) ,every 6 rats from the groups were sacrificed ,collected for plasma sample and the whole right lung. The plasma contents of Malondialdehyde(MDA) and superoxide dismutase(SOD),the wet/dry(W/D) weight ratio of the lung ,the activity of myeloperoxidase (MPO),and apoptotic index(AI)in lung tissue were determined . Histopathological study of the lung tissue were performed by light microscope and electron microscope.Results (1)The contents of MDA in plasma: Little change in plasma contents of MDA was measured in the three groups during the ischeima. In IR and A groups, MDA increased significantly compared with C group during reperfusion (P<0.05), but the increased level of MDA in the A group was obviously less than that in the IR group(P<0.05) .(2)The activity of SOD in plasma: SOD in both the IR group and A group were significantly lower in each same time point after ischemia- reperfusion than that in the C group (P<0.05) , but the decreased level of SOD in the A group was obviously less than that in the IR group(P<0.05).(3)The lung activity of MPO and W/D ratio: MPO and W/D ratio in both the IR group and A group were significantly higher compared with C group in each same time point ( P<0.05) ,but the increased level of MPO and W/D in the A group was obviously less than that in the IR group(P<0.05) .(4) The AI of lung tissue: The marked change of Apoptosis in lung tissue was not observed in the three groups during the ischeima. In IR and A groups, AI increased significantly compared with C group during reperfusion (P<0.05), but the increased level of AI in the A group was obviously less than that in the IR group(P<0.05). (5)Histological evaluation: In the process of ischemia-reperfusion ,the lung injury was aggravating progressively in the IR group;there was marked pulmonary capillary congestion, interstitial edema and leukocyte infiltration, intra-alveolar hemorrhage in the light microscopy; the electron microscopy showed that most of the mitochondria in the typeâ…¡cell were swollen and lamellar bodies were decreased or evacuated gradually. Compared with IR group, the degree of injury in A group was significantly ameliorated. Conclusions Amiloride treatment before ischemia could protect the lungs against the I/R induced injury by inhibiting the PMN infiltration,reducing the formation of oxyradical and decreasing the lung apoptotic .