A Study On Protective Effect And Mechanism Of Reduced Glutathione Hormone(GSH) On Oleic Acid Induced Acute Lung Injury(ALI) In Rabbits

Acute lung injury(ALI) is the early stage of acute respiratory distress syndrome(ADRS)pathologically and physiologically.They possess the same pathological and physiological changes.ALI/ARDS threaten mankind health due to their high incidence rate and case fatality rate.Currently,The studies on the prevention and treatment and their mechanism of ALI/ARDS are the hot spot.In this study,reduced glutathione hormone(GSH) was used to internve oleic acid(OA) induced acute lung injury(ALI) model in rabbits for the purpose of exploring the mechanism of action of ALI/ARDS and providing the experimental evidence in clinical treatment and further study.Objective:To explore the internal relations and value of the correlated indexes such as arterial partial pressure of oxygen (PaO2),wet/dry weight ratio of lung tissue,the concentration of tumor necrosis factor ( TNF-α) in serum and bronchoalveolar lavage fluid(BALF),the concentration of serous 8-isoprostane by means of detecting the dynamic changes of these indexes in ALI rabbit models.Reduced glutathione hormone(GSH) was used to internve oleic acid(OA) induced acute lung injury(ALI) model in rabbits for the purpose of comprehending the influence of G??n the indexes and exploring the protective effect and the potential mechanism of action.Methods:24 adult New-Zealand albino rabbit were randomly divided into 3 groups:normal control group(control group), ALI model group(model group) and GSH experimental group (experimental group),8 rabbits in average group.ALI models were prepared by intravenous injection of oleic acid(0.12mg/kg).Arterial partial pressure of oxygen (PaO2) and wet/dry weight ratio of lung tissue were monitored.The pathological changes of lung tissue and cells were observed with light microscope and electron microscope.Double antibody sandwich method(ABC-ELISA)was used to detect the concentration of tumor necrosis factor ( TNF-α) in serum and bronchoalveolar lavage fluid(BALF). enzyme immunoassay(EIA) was used to detect the concentration of serous 8-isoprostane.The measured value of the indexes were statistically statistics analyzed.Results:1 Arterial partial pressure of oxygen(PaO2) and oxygenation index(PaO2/FiO2) in model group and experimental group showed more significant decrease than that in control roup(P<0.01).Wet/dry weight ratio of lung tissue in model group and experimental group increased significantly than that in control group(P<0.01).Lung tissue damage existed in model group and experimental group pathologically and the degree in the former was more severe that in the latter.2 The concentration of tumor necrosis factor(TNF-α)in serum and bronchoalveolar lavage fluid(BALF) in model group and experimental group showed more significant increase than that in control group(P<0.01).The increased extent in experimental group was lower than that in model group(P<0.05).3 The concentration of serous 8-isoprostane in model group and experimental group showed more significant increas??an that in control group(P<0.01).The increased extent in experimental group was lower than that in model group(P<0.05).4 There was a linear relationship between the concentration of serous 8-isoprostane and the concentration of tumor necrosis factor(TNF-α)in serum.Conclusions:1 ALI rabbit models can be successfully reproduced by intravenous injection of oleic acid(OA)(0.12mg/kg).2 A disbalance state of oxidation and antioxidation system exists in ALI rabbit models.Isoprostanes may act as a sensitive, reliable and precise index reflecting the oxidative stress state in vivo.3 There was intimate relationship which is possibly a positive feedback between the oxidative stress state and inflammatory factors in ALI rabbit models.4 In the early stage of ALI,reduced glutathione hormone(GSH) can effectively palliate the oxidative stress state and decrease the released inflammatory factors in vivo.As an antioxidant,GSH has therapeutic effect on ALI to a certain extent.