Study Of Protective Effect Of Ambroxol/Amrinone On Lung Injury Induced By Ischemia/reperfusion

Objective To investigate the protective effect and mechanism ofAmbroxol/Amrinone protects against experimental lung ischemiareperfusion injury (IRI) in a situ hilar clamp model.Methods Left lung of rat was rendered ischemic for 90 minutes, andreperfused for up to 2 hours, as the model. thirty-two SD rats wererandomly divided into 4 groups with 8 rats each group: sham operationgroup(control group), I/R treatment group(I/R group), I/R and Ambroxoltreatment group(AMB group), I/R and Amrinone treatment group(AMR group).Rats of AMB group received Ambroxol (25mg/kg) Intraabdominally 30 minutesbefore ischemia and intravenously 5 minutes before reperfusion. Rats ofAMR group received Amrinone (10mg/kg) intravenously 30 minutes beforeischemia and 5 minutes before reperfusion. After 2 hours of reperfusion,blood-gas analysis, the serum level of IL-1β, IL-8 and TNF-αfromcarotid artery were delected. The wet/dry ratio of lung, the activity oferythrocuprein(SOD)and the content of malonaldehyde(MDA)were determinedand pathematology changes were observed in the left lung tissue by lightmicroscope.Results After 2 hours of reperfusion, blood-gas analysis, the serumlevel of IL-1β, IL-8 and TNF-αfrom carotid artery were delected. The wet/dry ratio of lung, the activity of erythrocuprein (SOD), the contentof malonaldehyde (MDA) and the activity of myeloperoxidase(MPO) weredetermined and pathematology changes were observed in the left lung tissue.Results After 2 hours of reperfusion, there were no significant changesof artery partial pressure of oxygen (PO₂) and partial pressure of carbondioxide (PCO₂) among four groups. The wet/dry ratio of lung, the activityof MPO (U/g) and the content of MDA (nmol/mgprot) of I/R group were (5.3±0.5),(1.30±0.26) and (0.66±0.16), significantly higher than thoseof the control group(P＜0.05).The administration of Ambroxol markedlyreduced the indexes above to (4.8±0.3),(0.93±0.40)å’Œ(0.51±0.07),respectively(P＜0.05).And the administration of Ambroxol markedlyraised the activity of SOD (U/mgprot) from (39.3±3.0) of I/R group to(49.9±7.3) (P＜0.05).The serum level of IL-1β(pg/ml),IL-8(pg/ml) andTNF-α(pg/ml) increased to (17.11±2.22),(15.07±3.56) and (22.97±3.22)after 2 hours reperfusion, markedly higher than that of control group.however, the Ambroxol administration could reduced the levelsignificantly to(17.11±2.22),(15.07±3.56)and(22.97±3.22)(P＜0.01).The wet/dry ratio of lung and the content of MDA (nmol/mgprot) ofAMR group were (4.8±0.2) and (0.51±0.09),respectively, significantlylower than those of the I/R group (P＜0.05). And the activity of SOD(U/mgprot) (54.7±6.8) of the administration of Amrinone significantlyhigher than those of the I/R group (P＜0.05). The serum level of IL-1 β(pg/ml),IL-8(pg/ml) and TNF-α(pg/ml) were respectively (17.11±2.22),(15.07±3.56) and (22.97±3.22) after 2 hours reperfusion of theadministration of Amrinone, markedly lower than those of I/R group.The results of pathology displayed that the construction of lungtissue was normal in all groups, and there was hyperemia in I/R group,but not in control group, AMB group and AMR group. However there were moreinflammatory cells in I/R group than the others groups.Conclusion Ambroxol/Amrinone protect the lung function againstI/R injury, which is related to resisting oxidation, inhibition ofactivating of neutrophils and inflammation factors release.