慢性呼吸衰竭患者血清MDA、SOD、GSH-Px水平的研究
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摘要
目的:本实验旨在①研究慢性呼吸衰竭患者治疗前后血清中MDA、SOD、GSH-Px水平的变化,探讨慢性呼吸衰竭患者体内的氧化应激状态以及这三种氧化应激指标在慢性呼吸衰竭发病过程中的作用和意义。②分析慢性呼吸衰竭患者血清中MDA、SOD、GSH-Px水平与动脉血气分析指标的相关性,探讨其在评估疾病严重程度及病情进展方面的临床意义。
方法:选取确诊慢性呼吸衰竭患者40例,其中Ⅰ型呼吸衰竭患者13例,Ⅱ型呼吸衰竭患者27例,对照组25例。分别于治疗前后留取静脉血,采用硫代巴比妥酸法测血清MDA,还原型谷胱甘肽消耗法测血清GSH-Px,黄嘌呤氧化酶法测血清SOD,同时测定受试者治疗前后动脉血气分析指标即动脉血氧分压(PaO_2)、动脉血二氧化碳分压(PaCO_2)。
结果:①SOD活力值:治疗前Ⅰ型呼吸衰竭组(56.53±11.61 U/ml)和Ⅱ型呼吸衰竭组(70.76±13.35 U/ml)与对照组(86.78±16.03U/ml)相比明显降低,差别有统计学意义(P＜0.01)。Ⅱ型呼吸衰竭明显高于Ⅰ型呼吸衰竭组,差别有统计学意义(P＜0.05)。治疗后Ⅰ型呼吸衰竭组(76.29±7.53 U/ml)和Ⅱ型呼吸衰竭组(81.08±13.98U/ml)仍低于对照组(92.12±15.15U/ml),差别有统计学意义,分别为(P＜0.01,P＜0.05)。Ⅰ型呼吸衰竭组和Ⅱ型呼吸衰竭组之间无统计学意义(P＞0.05)②GSH-Px活力值:与Ⅱ型呼吸衰竭组(129.15±18.70)和对照组(132.13±23.00)相比,治疗前Ⅰ型呼吸衰竭组(112.65±18.51)的活力明显降低,差别有统计学意义(P＜0.05)。Ⅱ型呼吸衰竭组和对照组之间差异无统计学意义(P＞0.05)。治疗后三组之间差别无统计学意义(P＞0.05)。③MDA值:治疗前Ⅰ型呼吸衰竭组(9.68±0.81nmol/ml)和Ⅱ型呼吸衰竭组(9.20±1.55nmol/ml)与对照组(7.64±1.47nmol/ml)相比明显增高,差别有统计学意义(P＜0.01)。Ⅰ型呼吸衰竭组和Ⅱ型呼吸衰竭组之间无统计学意义(P＞0.05)。治疗后三组之间差别无统计学意义(P＞0.05)。④PaO_2:三组患者治疗后有显著提高,差别有统计学意义(P＜0.01)⑤PaCO_2:Ⅱ型呼吸衰竭组治疗后(49.82±5.90mmHg)与治疗前(72.88±11.89mmHg)相比显著下降,差别有统计学意义(P＜0.01)。⑥Ⅰ型呼吸衰竭组患者动脉血气分析指标PaO_2与血清中MDA值呈负相关(r=-0.572,P＜0.05),与血清SOD活力值呈正相关(r=0.719,P＜0.01)⑦血清中MDA值与SOD活力值呈负相关(r=-0.943,P＜0.01),与GSH-Px也呈负相关(r=-0.355,P＜0.05)。
结论:(1)呼吸衰竭患者体内存在氧化应激反应,表现在氧化产物含量增高,抗氧化酶活性下降。(2)经过有效治疗后,机体氧化产物含量下降,抗氧化酶活性增高。(3)随着PaO_2的降低和SOD、GSH-Px活性的下降,MDA的含量增高,推测患者血清中MDA、SOD、GSH-Px水平的高低及其变化可能作为临床评估慢性呼吸衰竭患者病情严重程度及病情进展的参考指标。(4)同时提示一定范围内的高碳酸血症可以减轻氧化应激对慢性呼吸衰竭患者机体的损伤。
Objective The aim of this study is①by determinating the levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxides (GSH-Px)in the serum of patients with chronic respiratory failure before and after treatment,to explore the oxidative stress in patients with chronic respiratory failure and the role of the three markers in the pathophysiologic condition and clinical significance of chronic respiratory failure.②To analyze the correlation of the levels of MDA,SOD,GSH-Px of the serum and the arterial blood gases in patients with chronic respiratory failure,to investigate the clinical significance of the three markers in the evaluation of the severity and the progression of the disease.
Methods The study population consisted of 40 patients with chronic respiratory failure,including 13 patients with typeⅠ,27 patients with typeⅡand 25 controls. We measured the concentration of MDA through the method of Thiobarbituric acid-reaction,the activity of GSH-Px by the method of glutathion reductase consumption,the activity of SOD by the method of xanthine oxidase in the serum of all the participants before and after treatment.We obtained the arterial blood gases parameters partial pressure of oxygen in arterial blood(PaO_2),partial pressure of carbon dioxide in arterial blood(PaCO_2).
Results①SOD:The activity of SOD in typeⅠrespiratory failure(56.53±11.61 U/ml)and typeⅡrespiratory failure(70.76±13.35 U/ml)were significantly lower than that of controls(86.78±16.03U/ml)(P＜0.01)before treatment.It was significantly higher in typeⅡrespiratory failure than typeⅠrespiratory failure(P＜0.05).The activity of SOD in typeⅠrespiratory failure(76.29±7.53U/ml) and typeⅡrespiratory failure(81.08±13.98U/ml)remained significantly lower compared to controls(92.12±15.15U/ml)(P＜0.01,P＜0.05)after treatment.And there is no significance between typeⅠrespiratory failure and typeⅡrespiratory failure(P＞0.05).②GSH-Px:The activity of GSH-Px in typeⅠrespiratory failure(112.65±18.51)was lower compared to that of typeⅡrespiratory failure (129.15±18.70)and controls(132.13±23.00)(P＜0.05)before treatment.And there was no significance between typeⅡrespiratory failure and controls(P＞0.05).There were no significance among the three groups(P＞0.05)after treatment.③MDA:The concentration of MDA in typeⅠrespiratory failure(9.68±0.81nmol/ml)and typeⅡrespiratory failure(9.20±1.55nmol/ml)were significantly higher compared to that of controls(7.64±1.47nmol/ml)(P＜0.01)before treatment.And there was no significance between typeⅠrespiratory failure and typeⅡrespiratory failure (P＞0.05).There was no significance among the three groups(P＞0.05)after treatment.④PaO_2:The degree of PaO_2 in three groups after treatment are significantly higher than pretherapy(P＜0.01).⑤PaCO_2:The degree of PaCO_2 in typeⅡrespiratory failure after treatment(49.8±25.90mmHg)was significantly lower than pretherapy(72.88±11.89mmHg)(P＜0.01).⑥The degree of PaO_2 showed a significant negative correlation with the concentration of MDA(r=-0.572, P＜0.05),while positive correlation with the activity of SOD(r=0.719,P＜0.05)in typeⅠrespiratory failure.⑦The concentration of MDA showed a significant negative correlation with the activity of SOD(r=-0.943,P＜0.01)and GSH-Px(r=-0.355, P＜0.05).
Conclusion①There is obvious oxidative stress in patients with chronic respiratory failure,reflects as the increased level of oxidants and the decreased activity of antioxidants.②The level of oxidants were decreased and the activity of antioxidants were increased after the treatment of effective therapy.③There were correlation between the arterial blood gases parameters and the levels of MDA,SOD and GSH-Px in the serum,it was presumed that MDA,SOD and GSH-Px may be useful indexes in evaluating the severity and the degree of the progression in patients with chronic respiratory failure.④It was found that the hypercapnic acidosis in a degree may be decrease the damage of oxidative stress to the patients with chronic respiratory failure.
方法:选取确诊慢性呼吸衰竭患者40例,其中Ⅰ型呼吸衰竭患者13例,Ⅱ型呼吸衰竭患者27例,对照组25例。分别于治疗前后留取静脉血,采用硫代巴比妥酸法测血清MDA,还原型谷胱甘肽消耗法测血清GSH-Px,黄嘌呤氧化酶法测血清SOD,同时测定受试者治疗前后动脉血气分析指标即动脉血氧分压(PaO_2)、动脉血二氧化碳分压(PaCO_2)。
结果:①SOD活力值:治疗前Ⅰ型呼吸衰竭组(56.53±11.61 U/ml)和Ⅱ型呼吸衰竭组(70.76±13.35 U/ml)与对照组(86.78±16.03U/ml)相比明显降低,差别有统计学意义(P＜0.01)。Ⅱ型呼吸衰竭明显高于Ⅰ型呼吸衰竭组,差别有统计学意义(P＜0.05)。治疗后Ⅰ型呼吸衰竭组(76.29±7.53 U/ml)和Ⅱ型呼吸衰竭组(81.08±13.98U/ml)仍低于对照组(92.12±15.15U/ml),差别有统计学意义,分别为(P＜0.01,P＜0.05)。Ⅰ型呼吸衰竭组和Ⅱ型呼吸衰竭组之间无统计学意义(P＞0.05)②GSH-Px活力值:与Ⅱ型呼吸衰竭组(129.15±18.70)和对照组(132.13±23.00)相比,治疗前Ⅰ型呼吸衰竭组(112.65±18.51)的活力明显降低,差别有统计学意义(P＜0.05)。Ⅱ型呼吸衰竭组和对照组之间差异无统计学意义(P＞0.05)。治疗后三组之间差别无统计学意义(P＞0.05)。③MDA值:治疗前Ⅰ型呼吸衰竭组(9.68±0.81nmol/ml)和Ⅱ型呼吸衰竭组(9.20±1.55nmol/ml)与对照组(7.64±1.47nmol/ml)相比明显增高,差别有统计学意义(P＜0.01)。Ⅰ型呼吸衰竭组和Ⅱ型呼吸衰竭组之间无统计学意义(P＞0.05)。治疗后三组之间差别无统计学意义(P＞0.05)。④PaO_2:三组患者治疗后有显著提高,差别有统计学意义(P＜0.01)⑤PaCO_2:Ⅱ型呼吸衰竭组治疗后(49.82±5.90mmHg)与治疗前(72.88±11.89mmHg)相比显著下降,差别有统计学意义(P＜0.01)。⑥Ⅰ型呼吸衰竭组患者动脉血气分析指标PaO_2与血清中MDA值呈负相关(r=-0.572,P＜0.05),与血清SOD活力值呈正相关(r=0.719,P＜0.01)⑦血清中MDA值与SOD活力值呈负相关(r=-0.943,P＜0.01),与GSH-Px也呈负相关(r=-0.355,P＜0.05)。
结论:(1)呼吸衰竭患者体内存在氧化应激反应,表现在氧化产物含量增高,抗氧化酶活性下降。(2)经过有效治疗后,机体氧化产物含量下降,抗氧化酶活性增高。(3)随着PaO_2的降低和SOD、GSH-Px活性的下降,MDA的含量增高,推测患者血清中MDA、SOD、GSH-Px水平的高低及其变化可能作为临床评估慢性呼吸衰竭患者病情严重程度及病情进展的参考指标。(4)同时提示一定范围内的高碳酸血症可以减轻氧化应激对慢性呼吸衰竭患者机体的损伤。
Objective The aim of this study is①by determinating the levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxides (GSH-Px)in the serum of patients with chronic respiratory failure before and after treatment,to explore the oxidative stress in patients with chronic respiratory failure and the role of the three markers in the pathophysiologic condition and clinical significance of chronic respiratory failure.②To analyze the correlation of the levels of MDA,SOD,GSH-Px of the serum and the arterial blood gases in patients with chronic respiratory failure,to investigate the clinical significance of the three markers in the evaluation of the severity and the progression of the disease.
Methods The study population consisted of 40 patients with chronic respiratory failure,including 13 patients with typeⅠ,27 patients with typeⅡand 25 controls. We measured the concentration of MDA through the method of Thiobarbituric acid-reaction,the activity of GSH-Px by the method of glutathion reductase consumption,the activity of SOD by the method of xanthine oxidase in the serum of all the participants before and after treatment.We obtained the arterial blood gases parameters partial pressure of oxygen in arterial blood(PaO_2),partial pressure of carbon dioxide in arterial blood(PaCO_2).
Results①SOD:The activity of SOD in typeⅠrespiratory failure(56.53±11.61 U/ml)and typeⅡrespiratory failure(70.76±13.35 U/ml)were significantly lower than that of controls(86.78±16.03U/ml)(P＜0.01)before treatment.It was significantly higher in typeⅡrespiratory failure than typeⅠrespiratory failure(P＜0.05).The activity of SOD in typeⅠrespiratory failure(76.29±7.53U/ml) and typeⅡrespiratory failure(81.08±13.98U/ml)remained significantly lower compared to controls(92.12±15.15U/ml)(P＜0.01,P＜0.05)after treatment.And there is no significance between typeⅠrespiratory failure and typeⅡrespiratory failure(P＞0.05).②GSH-Px:The activity of GSH-Px in typeⅠrespiratory failure(112.65±18.51)was lower compared to that of typeⅡrespiratory failure (129.15±18.70)and controls(132.13±23.00)(P＜0.05)before treatment.And there was no significance between typeⅡrespiratory failure and controls(P＞0.05).There were no significance among the three groups(P＞0.05)after treatment.③MDA:The concentration of MDA in typeⅠrespiratory failure(9.68±0.81nmol/ml)and typeⅡrespiratory failure(9.20±1.55nmol/ml)were significantly higher compared to that of controls(7.64±1.47nmol/ml)(P＜0.01)before treatment.And there was no significance between typeⅠrespiratory failure and typeⅡrespiratory failure (P＞0.05).There was no significance among the three groups(P＞0.05)after treatment.④PaO_2:The degree of PaO_2 in three groups after treatment are significantly higher than pretherapy(P＜0.01).⑤PaCO_2:The degree of PaCO_2 in typeⅡrespiratory failure after treatment(49.8±25.90mmHg)was significantly lower than pretherapy(72.88±11.89mmHg)(P＜0.01).⑥The degree of PaO_2 showed a significant negative correlation with the concentration of MDA(r=-0.572, P＜0.05),while positive correlation with the activity of SOD(r=0.719,P＜0.05)in typeⅠrespiratory failure.⑦The concentration of MDA showed a significant negative correlation with the activity of SOD(r=-0.943,P＜0.01)and GSH-Px(r=-0.355, P＜0.05).
Conclusion①There is obvious oxidative stress in patients with chronic respiratory failure,reflects as the increased level of oxidants and the decreased activity of antioxidants.②The level of oxidants were decreased and the activity of antioxidants were increased after the treatment of effective therapy.③There were correlation between the arterial blood gases parameters and the levels of MDA,SOD and GSH-Px in the serum,it was presumed that MDA,SOD and GSH-Px may be useful indexes in evaluating the severity and the degree of the progression in patients with chronic respiratory failure.④It was found that the hypercapnic acidosis in a degree may be decrease the damage of oxidative stress to the patients with chronic respiratory failure.
引文
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[49]Laffey JG,O Croinin D,Mclonghlin P,et al.Permissive hypercapnia--role in protective lung ventilatory strategies.Intensive Care Med[J],2004,30:247-256.
[50]Shibata K,Cregg N,Engelberts D,et al.Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogeous xanthine oxidase.Am J Respir Crit Care Med,1998.158:1578-1584.
[51] Doerr CH,Gajic O,Berrios JC,et al.Hypercapnic acidosis impairs plasma membrane wound resealing in ventilator-injured lungs.Am J Respir Crit Care Med, 2005,171:1371-1377.
[52] Lang JD,Figueroa M,Sanders KD,et al .Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury.Am J Respir Crit Care Med,2005,171:147-157.
[53] Komatsu F,Kudoh H,Kagawa Y.Evaluation of oxidative stress and effectiveness of low-dose glucocorticoid therapy on exacerbation of chronic obstructive pulmonary disease. J Gerontol A Biol Sci Med Sci.2007,Apr;62(4):459-264.
[54] Sadowska AM,van Overveld FJ,G6recka D, et al.The interrelationship between markers of inflammation and oxidative stress in chronic obstructive pulmonary disease:modulation by inhaled steroids and antioxidant.Respir Med[J], 2005, Feb;99(2):241-249.
[55] Nadeem A,Chhabra SK,Masood A,et al.Increased oxidative stress and altered levels of antioxidants in asthma.J Allergy Clin Immunol,2003,111:72-78.
[56] Picado Deulofeu R,Lleonart R,et al.Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity.Allergy[J],2001,56:43-49.
[57] Schwartz J,Weiss ST.Relationship.between dietary vitamin C intake and pulmo nary function in the First National Health and Nutrition Examination Survey (NHA1NES I).Am J Clin Nutr,1994,59:110-114.
[58] Schwartz J,Weiss ST.Dfietary factors and their relation to respiratory symptoms. The Second National Health and Nutrition Examination Survey.Am J Epidemioi, 1990,132:67-76.
[59] Hu G,Cassano PA.Antioxidant Nutrients and Pulmonary Function:The Third National Health and Nutrition Examination Survey(NHANES III). Am J Epide moil,2000,151:975-981.
[60] La Vechia C,Decarli A,Pagano R. Vegetable consumption and risk of chronic dis -ease.Epidemiology, 1998,9:208-210.
[61] Minko T,Stefanov A, Pozharov V.Selected cont ribution: Lung hypoxia, antioxi -dant and antiapoptotic effects of liposome alpha-tocopherol.J Appl Physiol, 2002,93:1550-1560.
[62] Manna SK,Kuo MT,Aggarwal BB.Over expression of gamma glutamylcysteine synthetase suppresses tumor necrosis factor- induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1.Oncogene[J],1999, 18:4371-4382.
[63] Blesa S,Cortijo J,Miartinez-Losa M,et al.Effectiveness of oral N-acetylcysteine in a rat experimental model of asthma.Pharmacol Res[J],2002,45:135-140.
[64] Blesa S,Cortijo J,Mata M,et al.Oral N-acetyleysteine attenuates the rat pulmonary inflammatory response to antigen.Eur Respir J,2003,21:394-400.
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[66] Bagnato GF,Gulli S,De Pasquale R,et al.Efect of inhaled glutathione on airway response to 'Fog' challenge in asthmatic patients.Respiration[J],1999,66:518-21.
[1] Morcillo EJ,Estrela J,Cortijo J.Oxidative stress and pulmonary inflammation: pharmacological intervention with antioxidants.Pharmacol Ras[J], 1999,40:393-402.
[2] Messent M ,Sinclair DG,Quinlal GJ,et al .Pulmonary vascular permeability after cardio pulmonary by pass and its relationship to oxidative stress.Crit Care Med [J], 1997,25:425-429.
[3] Rahman I,Biswas SK,Jimenez LA,et al.Glutathione,stress responses,and redox signaling in lung inflammation.Antioxidant Redox signal [J], 2005,7:42-59.
[4] Rahman I, MacNee W. Role of transcription factors in inflammatory lung diseases. Thorax [J],1998,53:601—612.
[5] Pauweis RA,Buist AS,Calverley PM,et al.Global strategy for the diagnosis, manage ment, and prevention of chronic obstructive pulmonary disease.NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary.Am J Respir Crit Care Med,2001,163:1256-1276.
[6] Hoffmann A,Natoli G,Ghosh G.Transcritional regulation via the NF-kappaB signaling module.Oncogene[J], 2006,25:6706-6716.
[7] Pinhu L,Whitehead T,Evans T,et al.Ventilator-associated lung injury. Lancet[J], 2003,361:332-340.
[8] Grigoryev DN,Finigan JH,Hassoun P,et al.Seaching for gene conditates in acute lung injury.Crit Care [J],2004,8:440-447.
[9] Tian B,Briasiet AR.Identification of a nuclear factor kappaB-depentant gene network. Recent Prog Home Res [J],2003,58:95-130.
[10] Rahman I,MacNee W. Oxidative stress and regulation of glutathione in lung inflam-mation.Eur Respir J,2000,16:534-554.
[11] Chabot F,Mitchell JA,Gutteridge JMC,et al.Reactive oxygen species in acute lung injury.Eur Respir J,1998,l 1:745-757.
[12] Van der Vliet A,Cross CE.Oxidants,nitrosantsand the lung.Am J Med[J], 2000,109: 398-421
[13] Rahman I, Skwarska E, MacNee W, et al. Attenuation of oxidant/antioxidant imbalance during treatment of exacerbations of chronic obstructive pulmonary disease. Thorax[J],1997, Jun;52(6):565-8.
[14] Chow CW,Abreu MTH,Suzuki T,et al.Oxidative stress and acute lung injury.Am J Respir Cell Mol Biol,2003,29:427-431.
[15] Kelly FJ.Vitamins and respiratory disease:antioxidant micronutrients in pulmonary health and disease.Proc Nutr Soc[J],2005,64:510-526.
[16] Back EI,Frindt C,Nohr D,et al .Antioxidant deficiency in cystic fibrosis: when is the right time to take action?Am J Clin Nutr[J],2004,80:374-384.
[17] Kettle AJ,Chan T,Osberg I,et al.Myeloperoxidase and Protein Oxidation in the Airways of Young Children with Cystic Fibrosis. Am J Respir Crit Care Med, 2004, 170:1317-1323.
[18] Kinnula VL,Fattman CL,Tan RJ,et al.Oxidative stress in pulmonary fibrosis,A possible role for redox modulatory therapy.Am J Respir Crit Care Med,2005,172: 417-422.
[19] Kirkham P,Rahman I.Oxidative stress in asthma and COPD:antioxidants as a therapeutic strategy. Pharmacol Therape[J],2006,111:476-494.
[20] Nadeem A,Rai HG,Chhabra SK.Increased oxidative stress in acute exacerbations of asthma.J Asthma,2005,42:45-50.
[21] Komatsu F,Kudoh H,Kagawa Y.Evaluation of oxidative stress and effectiveness of low-dose glucocorticoid therapy on exacerbation of chronic obstructive pulmonary disease. J Gerontol A Biol Sci Med Sci.2007,Apr;62(4):459-64.
[22] Sadowska AM,van Overveld FJ, Gorecka D, et al. The interrelationship between markers of inflammation and oxidative stress in chronic obstructive pulmonary disease:modulation by inhaled steroids and antioxidant.Respir Med[J],2005.Feb, 99(2):241-9.
[23] Nadeem A,Chhabra SK,Masood A,et al.Increased oxidative stress and altered levels of antioxidants in asthma.J Allergy Clin Immunol,2003,111:72-78.
[24] Picado Deulofeu R,Lleonart R,et al.Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity.Allergy[J],2001,56:43-49.
[25] Schwartz J,Weiss ST.Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey(NHA1NES I).Am J Clin Nutr,1994,59:110-114.
[26] Schwartz J,Weiss ST.Dfietary factors and their relation to respiratory symptoms. The Second National Health and Nutrition Examination Survey.Am J Epidemioi, 1990,132:67-76.
[27] Hu G,Cassano PA.Antioxidant Nutrients and Pulmonary Function:The Third National Health and Nutrition Examination Survey(NHANES III).Am J Epide moil, 2000,151:975-981.
[28] La Vechia C,Decarli A,Pagano R. Vegetable consumption and risk of chronic disease. Epidemiology [J], 1998,9:208-210.
[29] Minko T,Stefanov A, Pozharov V.Selected contribution:Lung hypoxia, antioxidant and antiapoptotic effects of liposome alpha-tocopherol.J Appl Physiol,2002,93: 1550-1560.
[30] Manna SK,Kuo MT,Aggarwal BB.Over expression of gamma glutamylcysteine synthetase suppresses tumor necrosis factor- induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1. Oncogene[J],1999,18: 4371-4382.
[31] Blesa S,Cortijo J,Miartinez-Losa M,et al.Effectiveness of oral N-acetylcysteine in a rat experimental model of asthma.Pharmacol Res[J],2002,45:135-140.
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[49]Laffey JG,O Croinin D,Mclonghlin P,et al.Permissive hypercapnia--role in protective lung ventilatory strategies.Intensive Care Med[J],2004,30:247-256.
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[55] Nadeem A,Chhabra SK,Masood A,et al.Increased oxidative stress and altered levels of antioxidants in asthma.J Allergy Clin Immunol,2003,111:72-78.
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[57] Schwartz J,Weiss ST.Relationship.between dietary vitamin C intake and pulmo nary function in the First National Health and Nutrition Examination Survey (NHA1NES I).Am J Clin Nutr,1994,59:110-114.
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[59] Hu G,Cassano PA.Antioxidant Nutrients and Pulmonary Function:The Third National Health and Nutrition Examination Survey(NHANES III). Am J Epide moil,2000,151:975-981.
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[64] Blesa S,Cortijo J,Mata M,et al.Oral N-acetyleysteine attenuates the rat pulmonary inflammatory response to antigen.Eur Respir J,2003,21:394-400.
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[1] Morcillo EJ,Estrela J,Cortijo J.Oxidative stress and pulmonary inflammation: pharmacological intervention with antioxidants.Pharmacol Ras[J], 1999,40:393-402.
[2] Messent M ,Sinclair DG,Quinlal GJ,et al .Pulmonary vascular permeability after cardio pulmonary by pass and its relationship to oxidative stress.Crit Care Med [J], 1997,25:425-429.
[3] Rahman I,Biswas SK,Jimenez LA,et al.Glutathione,stress responses,and redox signaling in lung inflammation.Antioxidant Redox signal [J], 2005,7:42-59.
[4] Rahman I, MacNee W. Role of transcription factors in inflammatory lung diseases. Thorax [J],1998,53:601—612.
[5] Pauweis RA,Buist AS,Calverley PM,et al.Global strategy for the diagnosis, manage ment, and prevention of chronic obstructive pulmonary disease.NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary.Am J Respir Crit Care Med,2001,163:1256-1276.
[6] Hoffmann A,Natoli G,Ghosh G.Transcritional regulation via the NF-kappaB signaling module.Oncogene[J], 2006,25:6706-6716.
[7] Pinhu L,Whitehead T,Evans T,et al.Ventilator-associated lung injury. Lancet[J], 2003,361:332-340.
[8] Grigoryev DN,Finigan JH,Hassoun P,et al.Seaching for gene conditates in acute lung injury.Crit Care [J],2004,8:440-447.
[9] Tian B,Briasiet AR.Identification of a nuclear factor kappaB-depentant gene network. Recent Prog Home Res [J],2003,58:95-130.
[10] Rahman I,MacNee W. Oxidative stress and regulation of glutathione in lung inflam-mation.Eur Respir J,2000,16:534-554.
[11] Chabot F,Mitchell JA,Gutteridge JMC,et al.Reactive oxygen species in acute lung injury.Eur Respir J,1998,l 1:745-757.
[12] Van der Vliet A,Cross CE.Oxidants,nitrosantsand the lung.Am J Med[J], 2000,109: 398-421
[13] Rahman I, Skwarska E, MacNee W, et al. Attenuation of oxidant/antioxidant imbalance during treatment of exacerbations of chronic obstructive pulmonary disease. Thorax[J],1997, Jun;52(6):565-8.
[14] Chow CW,Abreu MTH,Suzuki T,et al.Oxidative stress and acute lung injury.Am J Respir Cell Mol Biol,2003,29:427-431.
[15] Kelly FJ.Vitamins and respiratory disease:antioxidant micronutrients in pulmonary health and disease.Proc Nutr Soc[J],2005,64:510-526.
[16] Back EI,Frindt C,Nohr D,et al .Antioxidant deficiency in cystic fibrosis: when is the right time to take action?Am J Clin Nutr[J],2004,80:374-384.
[17] Kettle AJ,Chan T,Osberg I,et al.Myeloperoxidase and Protein Oxidation in the Airways of Young Children with Cystic Fibrosis. Am J Respir Crit Care Med, 2004, 170:1317-1323.
[18] Kinnula VL,Fattman CL,Tan RJ,et al.Oxidative stress in pulmonary fibrosis,A possible role for redox modulatory therapy.Am J Respir Crit Care Med,2005,172: 417-422.
[19] Kirkham P,Rahman I.Oxidative stress in asthma and COPD:antioxidants as a therapeutic strategy. Pharmacol Therape[J],2006,111:476-494.
[20] Nadeem A,Rai HG,Chhabra SK.Increased oxidative stress in acute exacerbations of asthma.J Asthma,2005,42:45-50.
[21] Komatsu F,Kudoh H,Kagawa Y.Evaluation of oxidative stress and effectiveness of low-dose glucocorticoid therapy on exacerbation of chronic obstructive pulmonary disease. J Gerontol A Biol Sci Med Sci.2007,Apr;62(4):459-64.
[22] Sadowska AM,van Overveld FJ, Gorecka D, et al. The interrelationship between markers of inflammation and oxidative stress in chronic obstructive pulmonary disease:modulation by inhaled steroids and antioxidant.Respir Med[J],2005.Feb, 99(2):241-9.
[23] Nadeem A,Chhabra SK,Masood A,et al.Increased oxidative stress and altered levels of antioxidants in asthma.J Allergy Clin Immunol,2003,111:72-78.
[24] Picado Deulofeu R,Lleonart R,et al.Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity.Allergy[J],2001,56:43-49.
[25] Schwartz J,Weiss ST.Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey(NHA1NES I).Am J Clin Nutr,1994,59:110-114.
[26] Schwartz J,Weiss ST.Dfietary factors and their relation to respiratory symptoms. The Second National Health and Nutrition Examination Survey.Am J Epidemioi, 1990,132:67-76.
[27] Hu G,Cassano PA.Antioxidant Nutrients and Pulmonary Function:The Third National Health and Nutrition Examination Survey(NHANES III).Am J Epide moil, 2000,151:975-981.
[28] La Vechia C,Decarli A,Pagano R. Vegetable consumption and risk of chronic disease. Epidemiology [J], 1998,9:208-210.
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