慢性阻塞性肺疾病急性发作期患者氧化应激与全身炎症的研究
|
摘要
目的:探讨急性发作期慢性阻塞性肺疾病(AECOPD)患者氧化应激和全身炎症之间的关系。
方法:采用乙酸苯酯法检测40例AECOPD患者和30名正常对照者血清对氧磷酶(PON1)活性,用放射免疫法分别测定血清IL-6和IL-8水平;采用免疫投射比浊法测定血清C反应蛋白(CRP)的含量,用比色法分别检测血清丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH-Px)活性以及血清总抗氧化能力(TAC),并分析其相关性。
结果:(1)AECOPD组患者FEV_1为(1.34±0.80)L、FEV_1占预计值百分比(FEV_1%)(37.10±13.24)%分别与对照组(2.38±0.57)L、(87.50±16.40)%比较均有显著降低(P＜0.01);AECOPD组患者FVC(2.29±0.43)L、FVC占预计值百分比(FVC%)为(60.80±10.98)%分别与对照组(2.68±0.52)L、(98.40±11.20)%比较均有降低(P＜0.05);AECOPD组FEV_1/FVC%(55.23±7.49)%显著低于对照组(90.76±12.20)%(P＜0.01)。
(2)AECOPD组患者的体重指数(BMI)(21.90±3.95)kg/m~2、理想体重百分比(IBW%)(99.40±8.6)%、臂围(20.78±1.85)cm均小于正常对照组(23.15±3.36)kg/m~2、(111.50±9.20)%、(24.88±3.35)cm,差异均有统计学意义(P＜0.05)。AECOPD组患者的三头肌皮皱褶厚度(16.23±3.20)mm明显低于对照组(20.88±4.01)mm(P＜0.01)。
(3)AECOPD组患者血清PON1活性[(95.03±57.40)U/mL]、TAC[(9.86±3.19)NU/mL]与正常对照组[(136.0±60.50)U/mL]、[(18.42±8.23)NU/mL]相比较均明显降低(P＜0.01);GSH-Px活性[(128.46±28.27)U/mL]低于健康对照组[(186.60±39.50)U/mL](P＜0.05);血清MDA[(6.25±0.87)nmol/mL]较对照组[(3.65±0.54)nmol/mL]显著增高(P＜0.01)。
(4)AECOPD组患者血清CRP含量[(9.25±4.58)mg/L]、IL-6水平[(64.86±20.27)pg/mL]与正常对照组[(3.34±1.29)mg/L]、[(46.32±12.25)pg/mL]相比较显著增高(P＜0.01);IL-8水平[(2.63±0.75)ng/mL]与正常对照组[(1.82±0.67)ng/mL]比较有增高,差异有统计学意义(P＜0.05)。
(5)AECOPD组患者血清IL-6与三头肌皮皱褶厚度、BMI均呈显著相关(r值分别为-0.642、-0.486,P＜0.01),IL-6与呼吸困难评分呈正相关(r=0.330,P＜0.05);FEV_1占预计值百分比与C反应蛋白呈显著负相关(r=-0.511,P＜0.01)。
(6)AECOPD组患者BMI与GSH-Px呈正相关(r=0.382,P＜0.05)、与MDA呈显著负相关(r=-0.407,P＜0.01);FEV_1占预计值百分比与PON1活性呈正相关(r=0.434,P＜0.05),与MDA呈显著负相关(r=-0.800,P＜0.01),与TAC正相关(r=0.357,P＜0.05)。
(7)AECOPD组患者血清PON1活性与IL-8显著负相关(r=-0.589,P＜0.01);GSH-Px活性与IL-6呈负相关(r=-0.362,P＜0.05);MDA与CRP呈显著正相关(r=0.512,P＜0.01);TAC与IL-6呈显著负相关(r=-0.573,P＜0.01)。
结论:AECOPD患者存在有营养不良,全身炎症与全身氧化应激,全身炎症、全身氧化应激分别与营养不良以及肺功能恶化间存在相关。全身炎症与全身氧化应激之间存在正相关。
Objective:To explore the relationships between oxidative stress and systemic inflammation in patients with AECOPD.
Methods:Serum paraoxonase(PON1)activity was measured by phenyl acetate in 40 patients with AECOPD and 30 healthy persons.The IL-6 and IL-8 levels were detected by radioimmunoassay.The level of C-reactive protein(CRP)was measured by immune-reinforced turbidimetry.The malondialdehyde(MDA)level、glutathione peroxidase(GSH-Px)activity and total antioxidant capacity(TAC)were ed by chromatology.
Results:(1)FEV_1(1.34±0.80)L、FEV_1 predict(FEV_1%)(37.10±13.24)% in AECOPD group were significantly lower than control group(2.38±0.57)L、(87.50±16.40)%(P＜0.01);FVC(2.29±0.43)L、FVC predict(FVC%)(60.80±10.98)%in AECOPD group were lower than control group(2.68±0.52)L、(98.20±11.40)% (P＜0.05);FEV_1/FVC%(55.23±7.49)%in AECOPD group was obviously lower than control group(90.76±12.20)%(P＜0.01).
(2)The body mass index(BMI)(21.90±3.95)kg/m~2、Ideal body weight per predict(IBW%)(99.40±8.6)%,mid-arm muscle circumference(20.78±1.85)cm in AECOPD group were lower than control group(23.15±3.36)kg/m~2、(111.50±9.20)%、(24.88±3.35)cm(P＜0.05).The triceps skinfold thickness(16.23±3.20)mm was significantly lower than control group(20.88±4.01)mm(P＜0.01).
(3)The activity of serum PON1[(95.03±57.4)U/mL]、TAC[(9.86±3.19)NU/mL] in AECOPD group were significantly lower than control group[(136.0± 60.50)U/mL]、[(18.42±8.23)NU/mL](P＜0.01);The GSH-Px[(128.46±28.27)U/mL] in AECOPD group was lower than control grouop[(186.60±39.50)U/mL](P＜0.05). The serum MDA in AECOPD[(6.25±0.87)nmol/mL]was significantly higher than control group[(3.65±0.54)nmol/mL](P＜0.01).
(4)The level of CRP[(9.25±4.58)mg/L]、IL-6[(64.86±20.27)pg/mL]in AECOPD group were significantly higher than control group[(3.34±1.29)mg/L]、[(46.32±12.25)pg/mL](P＜0.01);The concentration of IL-8[(2.63±0.75)ng/mL]in AECOPD group was higher than in control group[(1.82±0.67)ng/mL](P＜0.05).
(5)In AECOPD group,the level of IL-6 was related to triceps skinfold thickness and BMI(r=-0.642,-0.486,P＜0.01);IL-6 was positively related to dyspnea scale(r=0.330,P＜0.05);The FEV_1%was negatively related to CRP (r=-0.511,P＜0.01).
(6)The BMI was related to GSH-Px activity(r=0.382,P＜0.05)and negatively related to MDA(r=-0.407,P＜0.01);The FEV_1%was positively related to PON1 activity(r=0.434,P＜0.05)and negatively related to MDA(r=-0.800,P＜0.01), positively related to TAC(r=0.357,P＜0.05).
(7)The PON1 was negatively related to IL-8(r=-0.589,P＜0.01);Serum GSH-Px activity was negatively related to IL-6(r=-0.362,P＜0.05);MDA was significantly positively related to C-reactive protein(r=0.512,P＜0.01);Total antioxidant capacity was negatively related to IL-6 in AECOPD patients(r=-0.573,P＜0.01).
Conclusions:There were malnutritional status、systemic inflammation and systemic oxidative stress in AECOPD group,the systemic inflammation and oxidative stress were both related to malnutritional status and the decrease of lung function in AECOPD.There were positive relationship between systemic inflammation and oxidative stress in patients with AECOPD.
方法:采用乙酸苯酯法检测40例AECOPD患者和30名正常对照者血清对氧磷酶(PON1)活性,用放射免疫法分别测定血清IL-6和IL-8水平;采用免疫投射比浊法测定血清C反应蛋白(CRP)的含量,用比色法分别检测血清丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH-Px)活性以及血清总抗氧化能力(TAC),并分析其相关性。
结果:(1)AECOPD组患者FEV_1为(1.34±0.80)L、FEV_1占预计值百分比(FEV_1%)(37.10±13.24)%分别与对照组(2.38±0.57)L、(87.50±16.40)%比较均有显著降低(P＜0.01);AECOPD组患者FVC(2.29±0.43)L、FVC占预计值百分比(FVC%)为(60.80±10.98)%分别与对照组(2.68±0.52)L、(98.40±11.20)%比较均有降低(P＜0.05);AECOPD组FEV_1/FVC%(55.23±7.49)%显著低于对照组(90.76±12.20)%(P＜0.01)。
(2)AECOPD组患者的体重指数(BMI)(21.90±3.95)kg/m~2、理想体重百分比(IBW%)(99.40±8.6)%、臂围(20.78±1.85)cm均小于正常对照组(23.15±3.36)kg/m~2、(111.50±9.20)%、(24.88±3.35)cm,差异均有统计学意义(P＜0.05)。AECOPD组患者的三头肌皮皱褶厚度(16.23±3.20)mm明显低于对照组(20.88±4.01)mm(P＜0.01)。
(3)AECOPD组患者血清PON1活性[(95.03±57.40)U/mL]、TAC[(9.86±3.19)NU/mL]与正常对照组[(136.0±60.50)U/mL]、[(18.42±8.23)NU/mL]相比较均明显降低(P＜0.01);GSH-Px活性[(128.46±28.27)U/mL]低于健康对照组[(186.60±39.50)U/mL](P＜0.05);血清MDA[(6.25±0.87)nmol/mL]较对照组[(3.65±0.54)nmol/mL]显著增高(P＜0.01)。
(4)AECOPD组患者血清CRP含量[(9.25±4.58)mg/L]、IL-6水平[(64.86±20.27)pg/mL]与正常对照组[(3.34±1.29)mg/L]、[(46.32±12.25)pg/mL]相比较显著增高(P＜0.01);IL-8水平[(2.63±0.75)ng/mL]与正常对照组[(1.82±0.67)ng/mL]比较有增高,差异有统计学意义(P＜0.05)。
(5)AECOPD组患者血清IL-6与三头肌皮皱褶厚度、BMI均呈显著相关(r值分别为-0.642、-0.486,P＜0.01),IL-6与呼吸困难评分呈正相关(r=0.330,P＜0.05);FEV_1占预计值百分比与C反应蛋白呈显著负相关(r=-0.511,P＜0.01)。
(6)AECOPD组患者BMI与GSH-Px呈正相关(r=0.382,P＜0.05)、与MDA呈显著负相关(r=-0.407,P＜0.01);FEV_1占预计值百分比与PON1活性呈正相关(r=0.434,P＜0.05),与MDA呈显著负相关(r=-0.800,P＜0.01),与TAC正相关(r=0.357,P＜0.05)。
(7)AECOPD组患者血清PON1活性与IL-8显著负相关(r=-0.589,P＜0.01);GSH-Px活性与IL-6呈负相关(r=-0.362,P＜0.05);MDA与CRP呈显著正相关(r=0.512,P＜0.01);TAC与IL-6呈显著负相关(r=-0.573,P＜0.01)。
结论:AECOPD患者存在有营养不良,全身炎症与全身氧化应激,全身炎症、全身氧化应激分别与营养不良以及肺功能恶化间存在相关。全身炎症与全身氧化应激之间存在正相关。
Objective:To explore the relationships between oxidative stress and systemic inflammation in patients with AECOPD.
Methods:Serum paraoxonase(PON1)activity was measured by phenyl acetate in 40 patients with AECOPD and 30 healthy persons.The IL-6 and IL-8 levels were detected by radioimmunoassay.The level of C-reactive protein(CRP)was measured by immune-reinforced turbidimetry.The malondialdehyde(MDA)level、glutathione peroxidase(GSH-Px)activity and total antioxidant capacity(TAC)were ed by chromatology.
Results:(1)FEV_1(1.34±0.80)L、FEV_1 predict(FEV_1%)(37.10±13.24)% in AECOPD group were significantly lower than control group(2.38±0.57)L、(87.50±16.40)%(P＜0.01);FVC(2.29±0.43)L、FVC predict(FVC%)(60.80±10.98)%in AECOPD group were lower than control group(2.68±0.52)L、(98.20±11.40)% (P＜0.05);FEV_1/FVC%(55.23±7.49)%in AECOPD group was obviously lower than control group(90.76±12.20)%(P＜0.01).
(2)The body mass index(BMI)(21.90±3.95)kg/m~2、Ideal body weight per predict(IBW%)(99.40±8.6)%,mid-arm muscle circumference(20.78±1.85)cm in AECOPD group were lower than control group(23.15±3.36)kg/m~2、(111.50±9.20)%、(24.88±3.35)cm(P＜0.05).The triceps skinfold thickness(16.23±3.20)mm was significantly lower than control group(20.88±4.01)mm(P＜0.01).
(3)The activity of serum PON1[(95.03±57.4)U/mL]、TAC[(9.86±3.19)NU/mL] in AECOPD group were significantly lower than control group[(136.0± 60.50)U/mL]、[(18.42±8.23)NU/mL](P＜0.01);The GSH-Px[(128.46±28.27)U/mL] in AECOPD group was lower than control grouop[(186.60±39.50)U/mL](P＜0.05). The serum MDA in AECOPD[(6.25±0.87)nmol/mL]was significantly higher than control group[(3.65±0.54)nmol/mL](P＜0.01).
(4)The level of CRP[(9.25±4.58)mg/L]、IL-6[(64.86±20.27)pg/mL]in AECOPD group were significantly higher than control group[(3.34±1.29)mg/L]、[(46.32±12.25)pg/mL](P＜0.01);The concentration of IL-8[(2.63±0.75)ng/mL]in AECOPD group was higher than in control group[(1.82±0.67)ng/mL](P＜0.05).
(5)In AECOPD group,the level of IL-6 was related to triceps skinfold thickness and BMI(r=-0.642,-0.486,P＜0.01);IL-6 was positively related to dyspnea scale(r=0.330,P＜0.05);The FEV_1%was negatively related to CRP (r=-0.511,P＜0.01).
(6)The BMI was related to GSH-Px activity(r=0.382,P＜0.05)and negatively related to MDA(r=-0.407,P＜0.01);The FEV_1%was positively related to PON1 activity(r=0.434,P＜0.05)and negatively related to MDA(r=-0.800,P＜0.01), positively related to TAC(r=0.357,P＜0.05).
(7)The PON1 was negatively related to IL-8(r=-0.589,P＜0.01);Serum GSH-Px activity was negatively related to IL-6(r=-0.362,P＜0.05);MDA was significantly positively related to C-reactive protein(r=0.512,P＜0.01);Total antioxidant capacity was negatively related to IL-6 in AECOPD patients(r=-0.573,P＜0.01).
Conclusions:There were malnutritional status、systemic inflammation and systemic oxidative stress in AECOPD group,the systemic inflammation and oxidative stress were both related to malnutritional status and the decrease of lung function in AECOPD.There were positive relationship between systemic inflammation and oxidative stress in patients with AECOPD.
引文
1 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2007年修订版).中华结核和呼吸杂志,2007,30(1):8-17.
2 Vendrell J,Broch M,Vilarrasa N,et al.Resistin,adiponectin,ghrelin,leptin,and proinflammatory cytokines:relationships in obesity.ObesityResearch,2004,12(6):965-971.
3 Sethi S,Muscarella K,Evans N,et al.Airway inflammation and etiology of acute excerbations of chronic bronchitis.Chest,2000,118:1557-1565.
4 Yen ML,Yang CY,Yen BL,et al.Increased high sensitivity C-reactive protein and neutrophil count are related to increased standard cardiovascular risk factors in healthy Chinese men.Int J Cardiol,2006,110(2):191-198.
5 La Du BN,Aviram M,Billecke S,et al.On the physical roles of the paraoxonase.Chem-Biol Inter,1999,120:379 -388.
6 Elkiran ET,Mar N,Aygen B,et al.Serum paraoxonase and arylesterase activates in patients with lung cancer in a Turkish population.BMC Cancer,2007,7:48-54.
7 Selek S,Cosar N,Kocyigit A,et al.PON1 activity and total oxidant status in patients with active pulmonary tuberculosis.Clin Biochem,2007,11:18-25.
8 Ekmekci OB,Donma O,Ekmekci H,et al.Plasma paraoxonase activities,lipoprotein oxidation,and trace element interaction in asthmatic patients.Biol Trace Elem Res,2006,111:41-52.
9 Selek S,Asian M,Horoz M,et al.Oxidative status and serum PON1 activity in beta-thalassemia minor.Clinical Biochemistry,2007,40:287-291.
10 Bodolay E,Seres I,Szodoray P,et al.Evaluation of paraoxonase activity in patients with mixed connective tissue disease.The journal of Rheumatology,2008,35:237-243.
11 Rahman J,Adcock IM.Oxidative stress and redox regulation of lung inflammation in COPD.Eur Respir J,2006,28(1):219-42.
12 Supinski GS,Callahan LA.Free radical-mediated skeletal muscle dysfunction in inflammatory conditions.J Appl Physiol,2007,102(5):2056-2063.
13 Wouters EF,Groenewegen KH,Dentener MA,et al.Systemic inflammation in chronic obstructive pulmonary disease.Proc Am Thorac Soc,2007,4:626-634.
14 Supinski G..Free radical induced respiratory muscle dysfunction.Molecular and Cellular Biochemistry,1998,179:99-110.
15 Drost EM,Skwarski KM,Souleda J,et al.Oxidative stress and airway inflammation in severe excerbations of COPD.Thorax,2005,60:293-300.
16 Mullen PG,Windsor ACJ,Walsh CJ,et al.Tumor necrosis factor-a and interleukin-6 selectively regulate neutrophil in vitro.J Surg Res,1995,58(2):124-130.
17 Biffl WL,Moore EE,Moore FA,et al.Interleukin-6 delays neutrophil apoptosis.Arch Surg,1996131(1):24-30.
18 Agusti A,Morla M,Sauleda J,et al.NF-κB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight.Thorax,2004,59:483-487.
19 Agusti AG,Sauleda J,Miralles C,et al.Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2002,166:485-489.
20 Chung KF.Cytokines in chronic obstructive pulmonary disease.Eur Respir J Suppl,2001,34:50-59.
21 Bucchioni E,Kharitonov SA,Allegra L,et al.High levels of interleukin-6 in the exhaled breath condensate of patients with COPD.Respir Med,2003,97(12):1299-1302.
22 de Torres JP,Cordoba-Lanus E,Lopez-Agullar C,et al.C-reactive protein levels and clinically important predictive outcomes in stable COPD patients:Eur Respir J,2006,27:902-907.
23 Broekhuizen R,Wouters EF,Creutzberg EC,et al.Raised CRP levels mark metabolic and functional impairment in advanced COPD.Thorax,2006,61:17-22.
24 Yende S,Waterer GW,Tolley EA,et al.Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects.Thorax,2006,61:10-18.
25 Boullier A,Hennuyer N,Tailleux A,et al.Increased levels of high density lipoprotein cholesterol are ineffective in inhibiting the development of immune responses to oxidized low density lipoprotein and atherosclerosis in transgenic rabbits expressing human apolipoprotein(apo)A- Ⅰ with sever hypercholesterolaemia.Clin Sci,2001,100(3):343-355:
26 Freese R,Alfthan G,Jauhiainen M,et al.High intakes of vegetables,berries,and apples combined with a high intake of linoleic or oleic acid only slightly affect markers of lipid peroxidation and lipoprotein metabolism in healthy subjects.Am J Clin Nutr,2002,76(5):950-960.
27 Sumegova K,Nagyova Z,Waczulikova I,et al.Activity of paraoxonase 1 and lipid profile in healthy children.Physiol.Res,2007,56:351-357.
28 Seo T,Pabwa P,McDuffie HH,et al.Interactive effect ofparaoxonase-1 Q192R polymorphism and smoking history on the lung function decline in grain workers.
29 Kim NS,Kang K,Cha MH,et al.Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans.Biochemical and Biophysical Research Communications,2007,364:157-162.
30 Can Demirdogen B,Turkanoglu A,Bek S,et al.Paraoxonase/arylesterase ratio,PON1 192Q/R polymorphism and PON1 status are associated with increased risk of ischemic stroke.Clin Biochem,2008,41(1-2):1-9.
31 Vendrell J,Broch M,Vilarrasa N,et al.Resistin,adiponectin,ghrelin,leptin and proinflammatory cytokines:relationships in obesity.Obesity Research,2004,12(6):965-971.
32 Isik B,Isik RS,Ceylan A,et al.Trace elements and oxidative stress in chronic obstructive pulmonary disease.Saudi Med J,2005,26(12):1882-1885.
33 曾高峰,刘康桐,丁翠芬等.吸烟对国人血清对氧磷酶活性的影响.临床心血管病杂志,2002,18(2):75-76.
34 Van Beurden WJ,Dekhuijzen PN,Harff GA,et al.Variability of exhaled hydrogen peroxide in stable COPD patients and matched healthy controls.Respiration,2003,69(3):211-216.
35 Pratico D,Basili S,Vieri M,et al.Chronic obstructive pulmonary disease associated with an increase in urinary levels of isoprostane F2a-Ⅲ:an index of oxidative stress.Am J Res Crtic Care Med,1998,158:1709-1714.
36 Hanta I,Kocabas A,Canacankatan N,et al.Oxidant-Antioxidant balance in patients with copd.Lung,2006,184:51-55.
37 刘卫,刘晓菊,余勤等.结核性胸膜炎患者DNA氧化损伤和脂质过氧化的研究.中华结核和呼吸杂志,2003,26(12):781-784.
38 Kluchova Z,Petrasova D,Joppa P,et al.The association between oxidative stress and obstructive lung impairment in patients with COPD.PhysiolRes,2007,56:51-56.
39 Schunemann HJ,Muti P,Freudenheim JL,et al.Oxidative stress and lung function.Am J Epidemiol,1997,146:939-948.
40 Nadeem A,Raj HG,Chhabra SK.Increased oxidative stress and altered levels of antioxidants in chronic obstructive pulmonary disease.Inflammation,2005,29(1):23-32.
41 Karadag F,Karul AB,Cildag O,et al.Determinants of BMI in patients with COPD.Respirology,2004,9:70-75.
42 MacNee W.Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease.Proc Am Thorac Soc,2005,2:50-60.
43 Mattson JP,Sun J,Murray DM,et al.Lipid peroxidation in the skeletal muscle of hamsters with emphysema.Pathophysiolgy,2002,8:215-221.
44 Sin DD,Man SF.Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular disease.The potential role of systemic inflammation in chronic obstructive pulmonary disease.Circulation,2003,107:1514-1519.
45 Ssdowska AM,Luyten C,Vints AM,et al.Systemic antioxidant defences during acute exacerbation of chronic obstructive pulmonary disease.Respirology,2006, 11:741-747.
46 Beeh KM,Beier J,Koppenhoefer N,et al.Increased glutathione disulfide and nitrosothiols in sputum supematant of patients with stable COPD.Chest,2004,126:1116-1122.
47 Kostikas K,Papatheodorou G;Psathakis K,et al.Oxidative stress in expired breath condensate of patients with COPD.Chest,2003,124:1373-1380.
48 Ssdowska AM,Van Overveld FJ,Gorecka D,et al.The inter-relationship between markers of inflammation and oxidative stress in chronic obstructive pulmonary disease:modulation by inhaled steroids and antioxidant.Respir Med,2005,99:241-249.
2 Vendrell J,Broch M,Vilarrasa N,et al.Resistin,adiponectin,ghrelin,leptin,and proinflammatory cytokines:relationships in obesity.ObesityResearch,2004,12(6):965-971.
3 Sethi S,Muscarella K,Evans N,et al.Airway inflammation and etiology of acute excerbations of chronic bronchitis.Chest,2000,118:1557-1565.
4 Yen ML,Yang CY,Yen BL,et al.Increased high sensitivity C-reactive protein and neutrophil count are related to increased standard cardiovascular risk factors in healthy Chinese men.Int J Cardiol,2006,110(2):191-198.
5 La Du BN,Aviram M,Billecke S,et al.On the physical roles of the paraoxonase.Chem-Biol Inter,1999,120:379 -388.
6 Elkiran ET,Mar N,Aygen B,et al.Serum paraoxonase and arylesterase activates in patients with lung cancer in a Turkish population.BMC Cancer,2007,7:48-54.
7 Selek S,Cosar N,Kocyigit A,et al.PON1 activity and total oxidant status in patients with active pulmonary tuberculosis.Clin Biochem,2007,11:18-25.
8 Ekmekci OB,Donma O,Ekmekci H,et al.Plasma paraoxonase activities,lipoprotein oxidation,and trace element interaction in asthmatic patients.Biol Trace Elem Res,2006,111:41-52.
9 Selek S,Asian M,Horoz M,et al.Oxidative status and serum PON1 activity in beta-thalassemia minor.Clinical Biochemistry,2007,40:287-291.
10 Bodolay E,Seres I,Szodoray P,et al.Evaluation of paraoxonase activity in patients with mixed connective tissue disease.The journal of Rheumatology,2008,35:237-243.
11 Rahman J,Adcock IM.Oxidative stress and redox regulation of lung inflammation in COPD.Eur Respir J,2006,28(1):219-42.
12 Supinski GS,Callahan LA.Free radical-mediated skeletal muscle dysfunction in inflammatory conditions.J Appl Physiol,2007,102(5):2056-2063.
13 Wouters EF,Groenewegen KH,Dentener MA,et al.Systemic inflammation in chronic obstructive pulmonary disease.Proc Am Thorac Soc,2007,4:626-634.
14 Supinski G..Free radical induced respiratory muscle dysfunction.Molecular and Cellular Biochemistry,1998,179:99-110.
15 Drost EM,Skwarski KM,Souleda J,et al.Oxidative stress and airway inflammation in severe excerbations of COPD.Thorax,2005,60:293-300.
16 Mullen PG,Windsor ACJ,Walsh CJ,et al.Tumor necrosis factor-a and interleukin-6 selectively regulate neutrophil in vitro.J Surg Res,1995,58(2):124-130.
17 Biffl WL,Moore EE,Moore FA,et al.Interleukin-6 delays neutrophil apoptosis.Arch Surg,1996131(1):24-30.
18 Agusti A,Morla M,Sauleda J,et al.NF-κB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight.Thorax,2004,59:483-487.
19 Agusti AG,Sauleda J,Miralles C,et al.Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2002,166:485-489.
20 Chung KF.Cytokines in chronic obstructive pulmonary disease.Eur Respir J Suppl,2001,34:50-59.
21 Bucchioni E,Kharitonov SA,Allegra L,et al.High levels of interleukin-6 in the exhaled breath condensate of patients with COPD.Respir Med,2003,97(12):1299-1302.
22 de Torres JP,Cordoba-Lanus E,Lopez-Agullar C,et al.C-reactive protein levels and clinically important predictive outcomes in stable COPD patients:Eur Respir J,2006,27:902-907.
23 Broekhuizen R,Wouters EF,Creutzberg EC,et al.Raised CRP levels mark metabolic and functional impairment in advanced COPD.Thorax,2006,61:17-22.
24 Yende S,Waterer GW,Tolley EA,et al.Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects.Thorax,2006,61:10-18.
25 Boullier A,Hennuyer N,Tailleux A,et al.Increased levels of high density lipoprotein cholesterol are ineffective in inhibiting the development of immune responses to oxidized low density lipoprotein and atherosclerosis in transgenic rabbits expressing human apolipoprotein(apo)A- Ⅰ with sever hypercholesterolaemia.Clin Sci,2001,100(3):343-355:
26 Freese R,Alfthan G,Jauhiainen M,et al.High intakes of vegetables,berries,and apples combined with a high intake of linoleic or oleic acid only slightly affect markers of lipid peroxidation and lipoprotein metabolism in healthy subjects.Am J Clin Nutr,2002,76(5):950-960.
27 Sumegova K,Nagyova Z,Waczulikova I,et al.Activity of paraoxonase 1 and lipid profile in healthy children.Physiol.Res,2007,56:351-357.
28 Seo T,Pabwa P,McDuffie HH,et al.Interactive effect ofparaoxonase-1 Q192R polymorphism and smoking history on the lung function decline in grain workers.
29 Kim NS,Kang K,Cha MH,et al.Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans.Biochemical and Biophysical Research Communications,2007,364:157-162.
30 Can Demirdogen B,Turkanoglu A,Bek S,et al.Paraoxonase/arylesterase ratio,PON1 192Q/R polymorphism and PON1 status are associated with increased risk of ischemic stroke.Clin Biochem,2008,41(1-2):1-9.
31 Vendrell J,Broch M,Vilarrasa N,et al.Resistin,adiponectin,ghrelin,leptin and proinflammatory cytokines:relationships in obesity.Obesity Research,2004,12(6):965-971.
32 Isik B,Isik RS,Ceylan A,et al.Trace elements and oxidative stress in chronic obstructive pulmonary disease.Saudi Med J,2005,26(12):1882-1885.
33 曾高峰,刘康桐,丁翠芬等.吸烟对国人血清对氧磷酶活性的影响.临床心血管病杂志,2002,18(2):75-76.
34 Van Beurden WJ,Dekhuijzen PN,Harff GA,et al.Variability of exhaled hydrogen peroxide in stable COPD patients and matched healthy controls.Respiration,2003,69(3):211-216.
35 Pratico D,Basili S,Vieri M,et al.Chronic obstructive pulmonary disease associated with an increase in urinary levels of isoprostane F2a-Ⅲ:an index of oxidative stress.Am J Res Crtic Care Med,1998,158:1709-1714.
36 Hanta I,Kocabas A,Canacankatan N,et al.Oxidant-Antioxidant balance in patients with copd.Lung,2006,184:51-55.
37 刘卫,刘晓菊,余勤等.结核性胸膜炎患者DNA氧化损伤和脂质过氧化的研究.中华结核和呼吸杂志,2003,26(12):781-784.
38 Kluchova Z,Petrasova D,Joppa P,et al.The association between oxidative stress and obstructive lung impairment in patients with COPD.PhysiolRes,2007,56:51-56.
39 Schunemann HJ,Muti P,Freudenheim JL,et al.Oxidative stress and lung function.Am J Epidemiol,1997,146:939-948.
40 Nadeem A,Raj HG,Chhabra SK.Increased oxidative stress and altered levels of antioxidants in chronic obstructive pulmonary disease.Inflammation,2005,29(1):23-32.
41 Karadag F,Karul AB,Cildag O,et al.Determinants of BMI in patients with COPD.Respirology,2004,9:70-75.
42 MacNee W.Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease.Proc Am Thorac Soc,2005,2:50-60.
43 Mattson JP,Sun J,Murray DM,et al.Lipid peroxidation in the skeletal muscle of hamsters with emphysema.Pathophysiolgy,2002,8:215-221.
44 Sin DD,Man SF.Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular disease.The potential role of systemic inflammation in chronic obstructive pulmonary disease.Circulation,2003,107:1514-1519.
45 Ssdowska AM,Luyten C,Vints AM,et al.Systemic antioxidant defences during acute exacerbation of chronic obstructive pulmonary disease.Respirology,2006, 11:741-747.
46 Beeh KM,Beier J,Koppenhoefer N,et al.Increased glutathione disulfide and nitrosothiols in sputum supematant of patients with stable COPD.Chest,2004,126:1116-1122.
47 Kostikas K,Papatheodorou G;Psathakis K,et al.Oxidative stress in expired breath condensate of patients with COPD.Chest,2003,124:1373-1380.
48 Ssdowska AM,Van Overveld FJ,Gorecka D,et al.The inter-relationship between markers of inflammation and oxidative stress in chronic obstructive pulmonary disease:modulation by inhaled steroids and antioxidant.Respir Med,2005,99:241-249.