【摘要】 目的观察羧甲司坦对慢性气道炎症大鼠肺组织中磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)和γ-谷氨酰半胱氨酸合酶(γ-GCS)表达的影响。方法将30只健康雄性SD大鼠随机分为对照组、模型组和羧甲司坦治疗组。模型组及羧甲司坦治疗组大鼠用气管内注入脂多糖和熏香烟法制成慢性气道炎症大鼠模型,羧甲司坦治疗组大鼠在第17～30天吸烟前30min给予羧甲司坦(500mg/kg)灌胃。计数各组大鼠支气管肺泡灌洗液(BALF)细胞,观察肺组织的病理变化;用免疫组织化学检测肺组织γ-GCS及磷酸化AKT(p-AKT)的表达水平;用逆转录聚合酶链反应(RT-PCR)检测PI3 K mRNA、γ-GCS mRNA的表达。结果与模型组比较,羧甲司坦治疗组大鼠支气管、肺组织中炎症浸润及BALF中中性粒细胞数明显降低(P<0.05),p-AKT蛋白、γ-GCS蛋白、PI3 K mRNA及γ-GCS mRNA的表达明显降低(P<0.05),谷胱甘肽(GSH)、活性氧(ROS)含量明显减少,总抗氧化能力明显上升(P<0.05)。结论羧甲司坦可能通过PI3K/AKT通路促进γ-GCS蛋白的表达,减轻被动吸烟大鼠肺部的炎症和氧化应激。更多还原

【Abstract】 Objective To observe effects of carbocisteine on phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT) and γ-glutamylcysteine synthetase(γ-GCS) expression in lung tissue of rats with chronic airway inflammation.Methods 30 healthy male SD rats were randomly divided into control group,model group and carbocisteine treatment group.Intratracheal instillation of lipopolysaccharide and cigarette smoking were resorted to establish rat models of chronic airway inflammation in model group and carbocisteine treatment group.Rats in carbocisteine treatment group were subjected to gastric irrigation with carbocisteine(500 mg/kg) 30 minutes before smoking from day 17 to day 30.Cells in bronchoalveolar lavage fluid(BALF) of rats in each group were counted,pathological changes of lung tissue were observed,immunohistochemical detection was adopted to detect the expression levels of γ-GCS and phosphorylated AKT(p-AKT) and reverse transcriptase-polymerase chain reaction(RT-PCR) was employed to detect the expression of PI3K mRNA and γ-GCS mRNA.Results Compared with model group,inflammatory infiltration in bronchial and lung tissue and neutrophils in BALF of rats in carbocisteine treatment group were significantly lessened(P<0.05),their p-AKT protein,γ-GCS protein,PI3K mRNA and γ-GCS mRNA expression were markedly decreased(P<0.05),and the contents of glutathione(GSH),reactive oxygen species(ROS) were obviously reduced,while that of total antioxidative capability significantly increased(P<0.05).Conclusion Carbocisteine probably reduces the inflammation and oxidative stress in lung of rats suffering from passive smoking through improving the expression of γ-GCS protein via PI3K/AKT pathway.更多还原