重症哮喘患儿中呼吸道谷胱甘肽内环境稳定发生改变：氧化应激的证据
2009/03/20
背景：重症哮喘的特征是持续的呼吸道炎症和活性氧生成增加。
目的：谷胱甘肽（GSH）是上皮细胞表层液体（ELF）中一种重要的抗氧化剂。我们假定重症哮喘患儿中呼吸道GSH内环境稳定发生改变，其特征是GSH水平降低和谷胱甘肽二硫化物（GSSG）水平升高。
方法：取65名重症哮喘患儿的支气管肺泡灌洗液，其中35名患儿基线呼吸道阻塞（FEV1<80%）。从患有心因性咳嗽（习惯性咳嗽）或经支气管镜检查确诊患有声带功能障碍的6名患儿和35名健康成人对照者获得对照数据。测定ELF中的GSH、GSSG和其他呼吸道氧化应激的决定因素，包括谷胱甘肽S转移酶（GST）、谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GPx）、丙二醛、8-异构前列腺素和H2O2。利用能斯特公式计算GSH和GSSG的ELF氧化还原电位。
结果：与对照者相比，重症哮喘患儿呼吸道GSH水平较低、GSSG水平升高，但两组比较GST、GR和GPx无显著差异。ELF中丙二醛、8-异构前列腺素和H2O2的水平升高。有呼吸道阻塞的重症哮喘患儿中GSH氧化最明显，ELF中GSH氧化还原电位上升证明了这点。
结论：重症哮喘患儿其ELF中的氧化应激生物标志物水平升高，氧化应激生物标志物水平升高与GSSG生成增加和GSH氧化还原电位向氧化状态转变有关。
（林江涛 审校）
Fitzpatrick AM, et al. J Allergy Clin Immunol. 2009 Jan;123(1):146-152.e8.
Fitzpatrick AM, et al. J Allergy Clin Immunol. 2009 Jan;123(1):146-152.e8.
Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress.
BACKGROUND: Severe asthma is characterized by persistent airway inflammation and increased formation of reactive oxygen species.
OBJECTIVES: Glutathione (GSH) is an important antioxidant in the epithelial lining fluid (ELF). We hypothesized that airway GSH homeostasis was altered in children with severe asthma and was characterized by decreased GSH and increased glutathione disulfide (GSSG) concentrations.
METHODS: Bronchoalveolar lavage was obtained from 65 children with severe asthma, including 35 children with baseline airway obstruction evidenced by FEV(1) <80%. Control data were obtained from 6 children with psychogenic (habit) cough or vocal cord dysfunction undergoing diagnostic bronchoscopy and 35 healthy adult controls. GSH, GSSG, and other determinants of airway oxidative stress including glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde, 8-isoprostane, and H(2)O(2) were measured in the ELF. The ELF redox potential was calculated from GSH and GSSG by using the Nernst equation.
RESULTS: Compared with controls, subjects with severe asthma had lower airway GSH with increased GSSG despite no differences in GST, GR, and GPx activities between groups. This was accompanied by increased malondialdehyde, 8-isoprostane, and H(2)O(2) concentrations in the ELF. GSH oxidation was most apparent in subjects with severe asthma with airway obstruction and was supported by an upward shift in the ELF GSH redox potential.
CONCLUSION: Children with severe asthma have increased biomarkers of oxidant stress in the ELF that are associated with increased formation of GSSG and a shift in the GSH redox potential toward the more oxidized state.
目的：谷胱甘肽（GSH）是上皮细胞表层液体（ELF）中一种重要的抗氧化剂。我们假定重症哮喘患儿中呼吸道GSH内环境稳定发生改变，其特征是GSH水平降低和谷胱甘肽二硫化物（GSSG）水平升高。
方法：取65名重症哮喘患儿的支气管肺泡灌洗液，其中35名患儿基线呼吸道阻塞（FEV1<80%）。从患有心因性咳嗽（习惯性咳嗽）或经支气管镜检查确诊患有声带功能障碍的6名患儿和35名健康成人对照者获得对照数据。测定ELF中的GSH、GSSG和其他呼吸道氧化应激的决定因素，包括谷胱甘肽S转移酶（GST）、谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GPx）、丙二醛、8-异构前列腺素和H2O2。利用能斯特公式计算GSH和GSSG的ELF氧化还原电位。
结果：与对照者相比，重症哮喘患儿呼吸道GSH水平较低、GSSG水平升高，但两组比较GST、GR和GPx无显著差异。ELF中丙二醛、8-异构前列腺素和H2O2的水平升高。有呼吸道阻塞的重症哮喘患儿中GSH氧化最明显，ELF中GSH氧化还原电位上升证明了这点。
结论：重症哮喘患儿其ELF中的氧化应激生物标志物水平升高，氧化应激生物标志物水平升高与GSSG生成增加和GSH氧化还原电位向氧化状态转变有关。
（林江涛 审校）
Fitzpatrick AM, et al. J Allergy Clin Immunol. 2009 Jan;123(1):146-152.e8.
Fitzpatrick AM, et al. J Allergy Clin Immunol. 2009 Jan;123(1):146-152.e8.
Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress.
BACKGROUND: Severe asthma is characterized by persistent airway inflammation and increased formation of reactive oxygen species.
OBJECTIVES: Glutathione (GSH) is an important antioxidant in the epithelial lining fluid (ELF). We hypothesized that airway GSH homeostasis was altered in children with severe asthma and was characterized by decreased GSH and increased glutathione disulfide (GSSG) concentrations.
METHODS: Bronchoalveolar lavage was obtained from 65 children with severe asthma, including 35 children with baseline airway obstruction evidenced by FEV(1) <80%. Control data were obtained from 6 children with psychogenic (habit) cough or vocal cord dysfunction undergoing diagnostic bronchoscopy and 35 healthy adult controls. GSH, GSSG, and other determinants of airway oxidative stress including glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde, 8-isoprostane, and H(2)O(2) were measured in the ELF. The ELF redox potential was calculated from GSH and GSSG by using the Nernst equation.
RESULTS: Compared with controls, subjects with severe asthma had lower airway GSH with increased GSSG despite no differences in GST, GR, and GPx activities between groups. This was accompanied by increased malondialdehyde, 8-isoprostane, and H(2)O(2) concentrations in the ELF. GSH oxidation was most apparent in subjects with severe asthma with airway obstruction and was supported by an upward shift in the ELF GSH redox potential.
CONCLUSION: Children with severe asthma have increased biomarkers of oxidant stress in the ELF that are associated with increased formation of GSSG and a shift in the GSH redox potential toward the more oxidized state.
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