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目的:研究慢性阻塞性肺疾病(COPD)大鼠血浆、肺、心、肝、和肾组织中氧化/抗氧化水平,及γ谷氨酰半胱氨酸合成酶(γ-GCS)活性及其表达在各器官组织中的差异和变化。方法:健康雄性Wistar大鼠14只,随机分COPD模型组和对照组,每组7只。采用每日熏香烟和两次气管内滴入脂多糖(LPS)法制作COPD大鼠模型。检测大鼠血浆、肺、心、肝和肾组织中还原型谷胱甘肽(GSH)、活性氧(ROS)、总抗氧化力(T-AOC)和γ-GCS活性。用逆转录-聚合酶链反应(RT-PCR)法检测肺、心、肝和肾组织中γ-GCS mRNA的表达。结果:COPD组大鼠心、肝中GSH、ROS、T-AOC和γ-GCS活性均显著增高(P均<0.05),但未显示出明显氧化/抗氧化失衡。肺中GSH和ROS提高,而T-AOC下降明显(P均<0.05),表明提高的GSH不足以抵御氧化作用,明显存在氧化/抗氧化失衡。血清中ROS增高,GSH和T-AOC下降明显,显示系统性氧化/抗氧化失衡。COPD大鼠肺组织γ-GCS mRNA表达较对照组显著增高(P<0.05),而心、肝、肾组织中γ-GCS mRNA表达与对照组无明显差异(P>0.05)。结论:COPD大鼠肺内存在氧化/抗氧化失衡,肺组织是γ-GCS表达的主要部位,在抗氧化损伤中可能发挥重要作用。
OBJECTIVE: To investigate the levels of oxidative / anti-oxidative and γ-glutamylcysteine synthase (γ-GCS) in plasma, lung, heart, liver and kidney of chronic obstructive pulmonary disease Express differences and changes in various organs and tissues. Methods: Fourteen healthy male Wistar rats were randomly divided into COPD model group and control group, with 7 rats in each group. COPD rat model was made by daily smoked cigarettes and twice by intratracheal instillation of lipopolysaccharide (LPS). The activities of GSH, T-AOC and γ-GCS in plasma, lung, heart, liver and kidney of rats were measured. The mRNA expression of γ-GCS in lung, heart, liver and kidney was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results: The activities of GSH, ROS, T-AOC and γ-GCS in the heart and liver of COPD rats were significantly increased (all P <0.05), but no obvious oxidative / antioxidant imbalance was found. The levels of GSH and ROS in the lung increased, while the T-AOC decreased significantly (all P <0.05), indicating that elevated GSH was not enough to resist the oxidative stress and there was a clear imbalance of oxidation / antioxidation. Serum ROS increased, GSH and T-AOC decreased significantly, showing systemic oxidative / antioxidant imbalance. The expression of γ-GCS mRNA in lung tissue of COPD rats was significantly higher than that of the control group (P <0.05), while the expression of γ-GCS mRNA in the heart, liver and kidney tissues was not significantly different from that of the control group (P> 0.05). CONCLUSIONS: Oxidative / anti-oxidative imbalance exists in the lungs of COPD rats. Lung tissue is the main site of γ-GCS expression and may play an important role in the anti-oxidative injury.