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Experimental Study On The Influence Of Chronic Alcohol Ingestion On Acute Lung Injury Induced By Oleic And Lipopolysaccharide

Posted on:2008-11-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:M L ZhuFull Text:PDF
GTID:1104360212487733Subject:Geriatrics
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objective Acute lung injury (ALI) is a kind of clinic syndrome with the character of permeable pulmonary edema and its serious phase is acute respiratory distress syndrome (ARDS), leading to respiratory failure and, in about 50% of the cases, death. Diverse biological insults, including sepsis, trauma, and aspiration, may result in acute lung injury even in previously healthy people without a history of pulmonary disease. In recent years ,a novel phenomenon has been observed, that a history of chronic alcohol abuse is associated with an increased prevalence and severity of acute respiratory distress syndrome (ARDS). Moreover, The mechanism underlying this correlation is unclear but may involve abnormal glutathione homeostasis. With the economic developed, the drinking rate increased in our country. According to annual alcohol consumption for pure alcohol , Chinese alcohol is the most used beverages of alcohol in china. Therefore ,we investigated the influence of chronic Chinese alcohol ingestion on the severity of acute lung injury (ALI) induced by oleic acid and lipopolysaccharide (LPS) in rats, and the changing of GSH,MDA and the levels of expression of AQP5, AQP4 and SP-A in the lung. We also observed the intervention effect of the traditional Chinese medicine membranous milkvetch root.Method (1)Male Sprague-Dawley rats weighing 180-200 g were divided into two groups: a chronic alcohol-exposure group and a water-control group. The alcohol group received 20% Chinese alcohol in their drinking water for six weeks. Body weights for both groups were recorded weekly. After 6 weeks, the rats were randomly divided into six groups, alcohol-drink and saline control rats(alcohol-control rats, AC group), alcohol-drink and lung injury rats(alcohol-injury rats, AI group), alcohol-injury and treatment rats(alcohol-treatment rats, AT group), water-drink and saline control rats(water-control rats, WC group), water-drink and lung injury rats(water-injury rats, WI group ), water-injury and treatment rats(water-treatment rats, WT group).During lung injury groups, the rats received intravenous injection of 0.15ml/kg oleic acid at first and celiac injection of 2mg/kg lipopolysaccharide two hours later. And the saline control rats received 0.9% saline injected the same dose and time as lung injury groups. (2)The parameters including PaO2, Wet to dry lung weight ratio (W/D), the protein content in the bronchoalveolar lavage fluid(BALF), and levels of γ-glutamylcysteinylglycine (GSH) and malonaldehyde (MDA) in the lung and liver constitution were observed.(3)The level of the AQP5, AQP4,and SP-A expressed in the lung or BALF were measured by western blot. And the immumohistometry method was used to localized the expression of AQP5 and AQP4 in the lung.Result (1)Compared to the saline group, the PaO2 decreased, W/ D and protein content in BALF increase , and the change were more deteriorated in alcohol-injury group.(2)GSH in liver and lung constitution were decreased in alcohol-control group rats compared to water-control rats, and GSH in lung and liver decreased more after having been injured, especially in alcohol-injury groups. MDA in liver constitution increased in alcohol-control group rats compared to water-control rats, after having been injured, MDA in lung and liver increased, especially in alcohol-injury groups. (3) The expression of AQP5 and SP-A protein in the lung and BALF were decreased after having been injured, especially in alcohol-injury groups. But the expression of AQP4 was not detected in the lung by western blot. By immunohistometrey method, we observed that AQP-4 was localized to the basolateral surfaces of small bronchi in the lung , and the expression were unchanged in our experiment. AQP5 were localized to the apical membrane of type I alveolar epithelial cells, and the express were decreased after injured, especially in alcohol-injury groups.(4) While in the drug intervened group,above mentioned indexes ameliorated, especially in ethanol group.Conclusion Chronic Chinese alcohol ingestion deteriorated the severity of the lung injury in the rat, the mechanism could be the imbalance of oxidation/antioxidation. TMembranous milkvetch root may improve the imbalance especially in the chronic alcohol ingestion rat.
Keywords/Search Tags:Acute lung injury, Glutathione, chronic alcohol ingestion, Membranous milkvetch root, Aquaporin 5, Surfactant association protein A
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