Susceptibility To Acute Lung Injury In Alcoholic Rats, And The Protective Effect Of ACEI On Acute Lung Injury

ObjectiveFirst,to investigate lung injury of alcoholic toxicity by studying the changes of interleukin-6(IL-6),vascular endothelial growth factor(VEGF) in plasma,lung lavage fluid and pathyology in the alcoholic rats.On the base,acute lung injury in-duced by lipopolysaccharide(LPS).To study chronic ethanol ingestion increased acute lung injury risk by observing the changes of IL-6,VEGF,monocyte chemotactic pro-tein 1 (MCP-1) and STAT₃ in the lung tissues.At last,to study the protect effect of cap-topril on acute lung injury in alcoholic rats by the results of blood gas,lung wet/dry ratio, lung pathologic and immunohistochemistry.MethodsAlcoholic rats medol was established by gavage.Some rats were in-jected endotoxin to reduce ALI/ARDS.Then the rats received captopril.The rats were divided into three test.Test one:normal control group and ethanol group.Test two(1) normal control group;(2)LPS group;(3) ethanol with LPS group.The rats of the last two tests were killed after 2 hours and 6 hours.Test three:(1) normal control group;(2)LPS group;(3) ethanol with LPS group;(4)Captopril(Cap) with LPS group;(5) Cap with LPS and ethanol group.Changes in physiological were observed.Lung wet/dry weight ratios(W/D) were recorded to evaluate lung injury.Histologyical changes of the lungs were evaluated by H.E stain,content of IL-6 and VEGF in serum and lung lavage fluid were measured by ELISA.Tissue's level of IL-6,VEGF and MCP-1 protein were further measured by ELISA.Lung expression of VEGF protein was assessed by immunohistochemistry. Lung tissue was obtained for determination of STAT₃ activity.ResultsTest one:(1) Artery blood gas analyses:Normal control group is no different with ethanol group.(2) Protein expression of IL-6 in plasma and BALF of ethanol group was significantly higher than control group(p＜0.01).Plasma's VEGF in ethanol group was significantly higher than that in control group(p＜0.01).But VEGF in BALF was lower than that in normal control group.(3) In ethanol group,there was slight inflammatory cells in alveolar than normal control group.Test two:(1) Artery blood gas analyses:PaO₂ and PaO₂/FiO₂ in LPS group and ethanol with LPS group were significantly lower,PaO₂ and PaO₂/FiO₂ in ethanol with LPS group were signi-ficantly lower than in LPS group.In 2h,pH and PaCO₂ in LPS group and ethanol with LPS group was significantly different than normal control group.But in LPS group was no different with ethanol with LPS group.(2) Lung wet,lung dry and lung wet/dry ratio: In LPS group and in ethanol with LPS group at every time were significantly increased than normal control group,especialy in 2h(p＜0.05).(3) Lung expression of VEGF protein in LPS group and in ethanol with LPS group was significantly decreased than in normal control group(p＜0.01),and in ethanol with LPS was significantly different with in LPS group(p＜0.01).IL-6 and MCP-1 is no expressed in normal control group.IL-6 in LPS group and in ethanol with LPS group was significantly increased than normal control group(p＜0.01).In 2h,ethanol with LPS group was significantly different from LPS group(p＜0.01).MCP-1 in LPS group and in ethanol with LPS group was significantly increased than normal control group(p＜0.01),ethanol with LPS group was signifi cantly different from LPS group(2h,p＜0.01.6h,p＜0.05).(4) STAT₃ activity was measured by western blotting:STAT₃ activity in LPS group and in ethanol with LPS group at every time point were higher than normal control group.Test three:(1) Atery blood gas analyses:After inject captopril,PaO₂,PaCO₂,pH and PaO₂/FiO₂ was better than LPS group and ethanol with LPS group,and PaO₂ and PaO₂/FiO₂ in ethanol with LPS group is lowest,especialy in 2h(p＜0.01).(2) Histologyical changes of the lung tissue:In normal control group,lung tissue is pink,it was no bleed,no edema,no necrose area.In ethanol with LPS group,lung tissue was red,lung volume was greater, and it was significantly bleed and edema.In Cap with ethanol and LPS group,it was slighter compare with in ethanol with LPS group.(3) Lung wet weight,lung dry weight and lung/dry ratios:In Cap with ethanol and LPS was better than LPS group and ethanol with LPS group.(4) Lung tissue expression of VEGF was significantly higher than LPS group and ethanol with LPS group(p＜0.01).MCP-1 was no express in normal control group,it was significantly higher in LPS group and ethanol with LPS group,but it was decreased when Cap was given.(5) immunohistochemistry:After captopril were given,in 6 hour,it can inhibit lung inflammation and may protect lung injury in ALI /ARDS.ConclusionTest one:(1) Chronic ethanol ingestion in a rat models may impair lung tissue. Level of inflammation factor is upmediate.Importantly,chronic ethanol in-gestion alone does not cause lung injury in our rat model.(2) Chronic ethanol ingestion may effect pulmonary function and may decrease gas-exchange function.Test two:(1) Chronic ethanol ingestion increased predispose rats to developing acute lung injury.(2) As experiment is shown:At the beginning of acute lung injury,that it was worse in 2h than in 6h.(3) JAK/STAT signaling pathway is functional in LPS and in chronic ethanol ingestion.Test three:(1) Captopril may protect lung tissue by inhibit angioension converting eneyme(ACE),and The protective effect of ACEI on acute lung injury in alcoholic rats.