N-乙酰半胱氨酸对心力衰竭兔中8-异前列腺素F2α与心功能的影响

目的:探讨N-乙酰半胱氨酸(NAC)对心力衰竭(心衰)兔的心功能和8-异前列腺素F2α的影响以及相关性。方法:以阿霉素复制心衰模型,随机分为心衰组和NAC组,药物干预4周,观测血流动力学指标、血清和心肌总抗氧化能力和8-异前列腺素F2α的变化,分析8-异前列腺素F2α与心功能的相关性,并观察NAC对上述指标的影响。结果:心衰组心功能指标左室收缩压、左室舒张末压、外周平均动脉压及左室峰压最大速率(±dp/dtmax)均比对照组明显下降(P0.01),NAC干预组上述心功能指标好转(P0.05)。心衰组总抗氧化能力均低于对照组(P0.01),NAC干预组总抗氧化能力升高(P0.05)。兔心衰后血清和心肌组织8-异前列腺素F2α水平明显高于对照组(P0.001),而NAC干预后8-异前列腺素F2α的含量较心衰组显著降低(P0.001)。血清和心肌组织的8-异前列腺素F2α水平之间存在着直线关系(F=220.59,P0.05),血清和心肌8-异前列腺素F2α水平与心功能指标左室舒张末压、±dp/dtmax呈显著直线相关,其中与LVEDP增高程度平行(P0.01),与±dp/dtmax均呈显著负相关(P0.01)。结论:心衰兔的心功能与氧化应激特异性标志物8-异前列腺素F2α有相关性,NAC可以降低心衰兔体内8-异前列腺素F2α的含量,升高其抗氧化能力,改善心功能。     

ACS患者8-异前列腺素F2α变化的临床意义

对急性冠脉综合征（ACS）患者进行了血浆8-异前列腺素F2α（8-iso-PGF2α）、血栓烷B2（TXB2）、6-酮前列腺素F1α（6-Keto-PGF1α）检测,结果显示,与正常对照组比较,患者组8-iso-PGF2α明显升高,与病情程度、TXB2呈正相关,与6-Keto-PGF1α呈负相关。说明患者前列腺素代谢严重失调,缺血再灌注损伤严重。     

ACS患者8-异前列腺素F2α变化的临床意义

对急性冠脉综合征(ACS)患者进行了血浆8-异前列腺素F2α(8-iso-PGF2α)、血栓烷B2(TXB2)、6-酮前列腺素F1α(6-Keto-PGF1α)检测,结果显示,与正常对照组比较,患者组8-iso-PGF2α明显升高,与病情程度、TXB2呈正相关,与6-Keto-PGF1α呈负相关.说明患者前列腺素代谢严重失调,缺血再灌注损伤严重.     

8-异前列腺素F2α与心血管疾病

8 异前列腺素F2 alpha(8 iso PGF2α)是近几年发现的前列腺素类代谢产物 ,是前列腺素F2α 的异构体(IsoprostaneF2α) ,是自由基损伤细胞膜脂质花生四烯酸发生脂质过氧化的产物。它不经过环氧化酶催化 ,属非酶性产物。 8 iso PGF2α是异前列腺F2α的主要和稳定的成分 ,具有     

2型糖尿病合并甲状腺功能减退对血清脂联素、8-异前列腺素F_(2α)的影响

目的探讨2型糖尿病(T2DM)合并甲状腺功能减退(甲减)对血清脂联素、8-异前列腺素F2α的影响。方法入选172例T2DM病人,收集病人年龄、性别、吸烟史、体质量指数(BMI)、血压、糖化血红蛋白、血脂、促甲状腺激素(TSH)等资料,根据甲状腺功能分为T2DM伴甲减组(73例)和单纯T2DM组(99例),采用ELISA法检测2组病人血清脂联素、8-异前列腺素F2α水平,分析甲状腺功能和脂联素、8-异前列腺素F2α的关系。结果2组病人年龄、性别、吸烟、BMI、血压、血糖、血脂差异无统计学意义(P0. 05)。T2DM伴甲减组病人8-异前列腺素F2α高于单纯T2DM组病人[(11. 17±3. 27) ng/m L比(7. 86±2. 01) ng/m L],脂联素[(10. 05±1. 86) ng/m L比(10. 70±1. 57) ng/m L]低于单纯T2DM组(P均0. 05))。多重线性回归调整了年龄、性别、BMI、吸烟、血压、糖化血红蛋白、血脂等混杂因素后显示,T2DM合并甲减是脂联素降低的危险因素(β=-0. 637),同时也是8-异前列腺素F2α水平升高的危险因素(β=3. 365)(均P0. 05)。T2DM合并甲减组中,Ln TSH和脂联素呈负相关(r=-0. 724),和8-异前列腺素F2α呈正相关(r=0. 738)(均P0. 05)。结论 T2DM合并甲减与脂联素及氧化应激有密切关联。     

格列齐特对2型糖尿病患者氧化应激状态的影响

观察格列齐特对糖尿病患者硝化酪氨酸（NT）、12（S）-羟基二十碳四烯酸[12（S）-HETE]和8-异-前列腺素F2α（8-iso-PGF2α）水平的影响，并与对照组比较。发现糖尿病组NT、12（S）-HETE高于对照组，治疗后有所下降。     

8-异前列腺素F2α与高血压及阻塞性睡眠呼吸暂停低通气综合征

8-异前列腺素F2α(8-iso-prostaglandin F2α,8-iso-PGF2α)是机体内脂质过氧化反应的特异性产物,是评价氧化应激和脂质过氧化反应理想的生物学指标.阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)是一种常见的睡眠呼吸紊乱疾病,常并发高血压病.8-iso-PGF2α不仅能敏感反映()SAHS的氧化应激状态,并可能为OSAHS并发高血压的预测因子,现就8-iso-PGF2α与高血压及OSAHS的相关性作一综述.     

8-iso-PGF2α与心血管疾病的研究

近几年发现评价氧化应激(OS)程度最理想的生化指标为8-异前列腺素F2α(8-iso-prostaglandin F2α,8-iso-PGF2α),其能够特异、准确地反映氧化应激后的脂质过氧化作用,机体产生8-iso-PGF2α的机制、过程与过氧化损伤关系极为密切,可以很好反应机体内的氧化应激水平,是评价体内OS的金标准[1],研究已证明血尿8-iso-PGF2α水平与心血管疾病(冠心病、高血压、心力衰竭、糖尿病等疾病)关系密切。     

呼出气冷凝液中8-异前列腺素水平检测对咳嗽变异性哮喘的临床意义

目的探讨8-异前列腺素检测对诊治咳嗽变异性哮喘(CVA)的临床意义。方法选取50例CVA患者和30例健康对照纳入研究,所有受试者测定呼出气冷凝液中8-异前列腺素水平并进行肺功能检测。结果与健康人群相比,CVA患者EBV中8-iso-PG水平显著升高(P0.01);治疗前后比较,CVA患者EBV中8-iso-PG水平明显降低(P0.01),而FEV1%检测差异无统计学意义。EBV中8-iso-PG水平与FEV1%检测值之间无相关性(r=-0.17,P0.05)。结论 EBC中8-iso-PG检测可直观反映CVA患者存在的气道氧化应激状态,并能较好的预测治疗敏感性,从而有助于CVA患者的早期诊断和疗效预判。     

利用混合呼出气氧浓度估算实际吸入氧浓度

目的 探讨利用混合呼出气氧浓度(expired oxygen concentraion,FEO2)估算吸入氧浓度(inspired oxygen concentration,F1 O2)的准确性和可行性,从而为进行氧疗的危重患者计算氧合指数(oxygen index,OI)及病情评估提供依据和实用的方法.方法 选择8名健康对照者、8例中-重度慢性阻塞性肺疾病(COPD)稳定期患者、7例ICU插管机械通气患者,吸入3种不同已知浓度的空氧混合气体,同步收集呼出气,分析F1O2与FEO2的相关性.结果 通过同步检测FEO2和F1O2,分析两者的关系,建立回归方程:健康对照组、COPD组及ICU插管机械通气患者组的参数估计方程分别是:F1O2=4.02+ 1.02 FE O2-0.07 RR( R2=0.999,SE=0.659,P=0.000);F1 O2=3.51+ 1.02 FE O2-0.09RR ( R2=1.000,SE =0.477,P =0.000);FI O2=1.59+ 1.00FEO2(R2=1.000,SE=0.436,P=0.000),FEO2可以很好预测F1O2,两者相关性高,重复性好.结论 通过收集呼出气测定FEO2,可准确计算出F1O2.不同试验组F1O2预测方程的决定系数非常高,标准误差小,重复性好,适合于临床评价F1O2及OI.     

Improved method of plasma 8-Isoprostane measurement and association analyses with habitual drinking and smoking

INTRODUCTIONA number of studies have revealed that oxidative stress plays important roles in the pathogenesis of various dis-eases, such as cancer, diabetes and atherosclerosis[1,2]. The 8-isoprostane present in biological fluids is produced from arachido…     

BAL Fluid 8-Isoprostane Concentrations in Eosinophilic Bronchitis and Asthma

Background. Oxidative stress has an important role in the pathophysiology of asthma. But oxidative stress of airway has not been assessed in patients with nonasthmatic eosinophilic bronchitis (EB). 8-epi-prostaglandin F2alpha (8-isoprostane) is a biomarker of oxidative stress. Objectives. We sought to determine whether oxidative stress (measured by 8-isoprostane) occurs in EB and whether 8-isoprostane is associated with airway function in EB and asthma. Methods. We measured 8-isoprostane concentrations in the bronchoalveolar lavage (BAL) fluid from 11 subjects with EB, 10 subjects with asthma, and 9 healthy control subjects. 8-isoprostane was measured by enzyme immunoassays. Results. We found that BAL fluid 8-isoprostane concentrations were raised both in EB and asthma. The median concentrations of 8-isoprostane in BAL fluid were significantly higher in subjects with asthma (12.78 pg/mL) when compared with EB (8.34 pg/mL) and healthy control subjects (5.07 pg/mL). Conclusions. Our study shows that oxidative stress is increased significantly in asthmatic subjects and the degree of oxidative stress in EB subjects is milder than that in asthma, as reflected by 8-isoprostane concentrations in the BAL fluid. The difference in airway function observed in subjects with EB and asthma could be associated with different elevation in 8-isoprostane concentration in the airways.     

Associations of isoprostanes-related oxidative stress with surrogate subclinical indices and angiographic measures of atherosclerosis

OBJECTIVES: Cardiovascular diseases are the most common cause of death in the world. Oxidative stress has been proved to play a role in atherosclerotic diseases and 8-isoprostane is one of the most valid markers of in-vivo oxidative stress. We aimed to investigate the 8-isoprostane levels in relation to surrogate and direct angiographic indexes of atherosclerosis. METHODS: Urinary 8-isoprostane levels were measured and a B-mode carotid ultrasound examination was performed in 100 consecutive patients scheduled for coronary angiography. RESULTS: In patients with angiographic coronary artery disease (CAD) urinary 8-isoprostane levels were significantly (P<0.001) higher than in patients without CAD (68.75+/-5.5 vs. 38.27+/-3.7 pg/ml). Moreover, 8-isoprostane levels of patients with increased carotid intima media thickness (CIMT) were higher (P<0.001) than in patients with normal CIMT values (75.12+/-6.4 vs. 38.72+/-2.7 pg/ml). Moreover log(8-isoprostane) levels were significantly correlated with maximum and mean CIMT values (P<0.001) and across univessel and multivessel CAD groups levels of log(8-isoprostane) showed a significantly (P<0.001) increasing trend. Logistic regression analysis revealed that 8-isoprostane levels were an independent predictor for both intima-media thickening and angiographic CAD. CONCLUSION: These findings indicate that elevated urinary levels of 8-isoprostane are associated with both subclinical atherosclerosis and manifest CAD. The results therefore support the hypothesis that isoprostanes-related oxidative stress is involved in the whole atherosclerotic process.     

Serum levels of 8-isoprostane, a marker of oxidative stress, are elevated in patients with systemic sclerosis

OBJECTIVE: To determine serum levels and clinical correlation of 8-isoprostane, which is produced in vivo through free radical-catalysed peroxidation of arachidonic acid and reflects oxidative stress, in patients with systemic sclerosis (SSc). METHODS: Serum 8-isoprostane levels from 32 patients with diffuse cutaneous SSc (dSSc) and 25 patients with limited cutaneous SSc (lSSc) were examined by enzyme-linked immunosorbent assay. RESULTS: Serum 8-isoprostane levels were elevated in dSSc and lSSc patients by 75-fold compared with normal controls (n=32). Serum 8-isoprostane levels correlated negatively with pulmonary function, such as percentage vital capacity and diffusion capacity for carbon monoxide, and correlated positively with renal vascular damage determined by colour flow Doppler ultrasonography. Serum 8-isoprostane levels also correlated positively with serum levels of IgG and anti-agalactosyl IgG autoantibody. CONCLUSION: Increased 8-isoprostane levels correlated with the severity of pulmonary fibrosis, the extent of renal vascular damage and immunological abnormalities in SSc, suggesting that enhanced oxidative stress is related to the development of SSc.     

Urinary 8-isoprostane levels can indicate the presence, severity and extent of angiographic coronary artery disease

BACKGROUND: Atherosclerotic coronary artery disease is the leading cause of death worldwide. Oxidative stress is one of the key elements in the pathogenesis of atherosclerosis. Isoprostanes are established markers of oxidative stress. The aim of this study was to investigate the association of urinary 8-isoprostane levels with the presence and severity of coronary artery disease (CAD) assessed by a validated scoring system. METHOD: Urinary 8-isoprostane levels were measured in 100 consecutive patients scheduled for coronary angiography. Extent and severity of CAD were assessed by modified Gensini scores. RESULTS: In patients with CAD, 8-isoprostane levels were higher (P < 0.001) than in patients without CAD (68.75 +/- 5.5 vs. 38.27 +/- 3.7 pg/ml). The levels of 8-isoprostane correlated with the number of risk factors (P < 0.001) and significantly increased in relation with the number of diseased vessels (P < 0.001). A significant (P < 0.001) correlation was found between 8-isoprostane levels and Gensini scores (r = 0.496), and a stepwise elevation in 8-isoprostane levels was observed across the increasing tertiles of the Gensini scores (P < 0.001). The multivariate logistic regression analysis revealed that 8-isoprostane was an independent predictor (odds ratio: 7.19 and P = 0.007) associated with angiographic CAD. CONCLUSION: These results confirm the role of oxidative stress in the atherosclerotic process. Urinary 8-isoprostane levels reflect the extent and severity of CAD and they may provide additional information for risk assessment in patients with suspected CAD.     

The relationship between oxidative stress and acid stress in adult patients with mild asthma

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of asthma. Interestingly, a low airway pH and a high concentration of 8-isoprostane, a marker of oxidative stress, has been reported to cause inflammatory airway diseases. However, the relationship between these 2 markers and pulmonary function has not been determined in mild asthma patients. METHODS: pH and 8-isoprostane concentration were measured in exhaled breath condensate (EBC) from patients with mild asthma (n = 44) and healthy subjects (n = 20). The relationship between acid stress (pH) and oxidative stress (8-isoprostane) was then analyzed, along with the relationships between these 2 markers and lung function. RESULTS: The median (interquartile range [IQR]) pH of EBC was significantly lower in asthma patients than in control subjects (7.53 [7.41-7.68] vs 7.70 [7.62-7.74], P < .05), while the median (IQR) 8-isoprostane concentration of EBC was significantly higher in asthma patients than control subjects (16.2 [11.7-19.1] vs 3.5 [2.6-7.9] pg/mL, P < .05). There was no correlation between pH and 8-isoprostane concentration. Furthermore, lung function was not correlated with either pH or 8-isoprostane concentrations in EBC. CONCLUSIONS: Acid stress and oxidative stress assessed by pH and 8-isoprostane concentration, respectively, in EBC did not show parallel changes associated with asthma and were not correlated with lung function in asthma patients. These 2 stress factors may have different roles in the pathogenesis of asthma.     

Quantitative analysis of 8-isoprostane and hydrogen peroxide in exhaled breath condensate.

Exhaled breath condensate (EBC) provides a noninvasive means of sampling the lower respiratory tract. Collection of EBC might be useful in the assessment of airway oxidative stress in smokers. The aim of this study was to determine 8-isoprostane and hydrogen peroxide levels in EBC, and, in addition, to investigate the reproducibility of these measurements. EBC samples were collected from 12 healthy male smokers at three time points within 1 week. 8-isoprostane and H2O2 were measured in nonconcentrated EBC using immunochemical and colorimetric assays, respectively. 8-isoprostane and H2O2 were detected in only 36 and 47% of all EBC samples, respectively. It was not possible to calculate the within-subject variation in a reliable manner since only three of the 12 smokers exhibited detectable 8-isoprostane concentrations on all three occasions (mean 4.6 pg x mL(-1); range 3.9-7.7 pg x mL(-1)), whereas H2O2 could not be detected on all three occasions in any of the smokers. Spiking experiments revealed a recovery of 83.5-109.5% for 8-isoprostane and 69.9-129.0%, for H2O2 in fresh EBC samples. It was concluded that levels of 8-isoprostane and hydrogen peroxide cannot be reproducibly assessed in exhaled breath condensate from healthy smokers because of their low concentration and/or the lack of sensitivity of the available assays.     

Association between lipid peroxidation and inflammation in obstructive sleep apnoea.

In the present study, the authors examined the relationship between lipid peroxidation and inflammation in patients with obstructive sleep apnoea (OSA). A total of 40 obese patients with OSA were studied, along with 18 obese and 12 lean subjects without OSA. Overnight excretion of 8-isoprostane in urine and serum levels of high-sensitivity C-reactive protein (hsCRP) were measured. In addition, the effects of 3 months' treatment with nasal continuous positive airway pressure (nCPAP) were studied in 20 obese patients with moderate-to-severe OSA. Overnight urinary excretion of 8-isoprostane and serum levels of hsCRP were significantly higher in patients with moderate-to-severe OSA compared with patients with mild OSA and obese or lean subjects without OSA. Overnight urinary excretion of 8-isoprostane significantly correlated with apnoea-hypopnoea index, duration of hypoxia during sleep, body mass index, and serum levels of hsCRP in patients with OSA. The severity of OSA was an independent factor predicting the urinary excretion of 8-isoprostane. nCPAP significantly decreased urinary excretion of 8-isoprostane and serum levels of hsCRP. In conclusion, these results suggest that both obstructive sleep apnoea severity and obesity can independently contribute to elevations in urinary excretion of 8-isoprostane. Therefore, obstructive sleep apnoea may increase the risks of cardiovascular morbidity in obese patients.     

Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of chronic liver diseases. The plasma level of 8-isoprostane, a product of lipid peroxidation, is a marker of oxidative stress in vivo. The aim of the present study was to clarify whether the degree of lipid peroxidation, as measured by the plasma level of 8-isoprostane, influences the progression of chronic liver diseases and hepatocarcinogenesis. METHODS: Plasma 8-isoprostane levels were investigated in 14 patients with non-alcoholic fatty liver disease (NAFLD), 75 with chronic hepatitis C (CH-C), 14 with cured CH-C, 14 with HCV-positive hepatocellular carcinoma (HCC-C) and 38 healthy volunteers. 8-Isoprostane was measured by enzyme immunoassay after affinity column purification. RESULTS: Plasma 8-isoprostane was significantly elevated in NAFLD (11.9 [3.8-56.8] pg/mL), CH-C (10.1 [4.2-134.5] pg/mL) as compared to controls (6.3 [3.6-11.1] pg/mL). Plasma 8-isoprostane values were positively correlated with body mass index in NAFLD (P < 0.05) and with total cholesterol in cured CH-C (P < 0.01). 8-Isoprostane levels were not significantly related to sex, age, biochemical data or iron metabolism markers in all liver diseases. In addition, after the administration of peg-interferon, the values of 8-isoprostane improved in almost all patients, reaching values of healthy subjects. CONCLUSIONS: 8-Isoprostane values are elevated in patients with NAFLD and CH-C as compared to healthy controls. Oxidative stress caused by increased lipid peroxidation is involved in the pathogenesis of NAFLD and CH-C.     

Low-density lipoprotein reduction by simvastatin is accompanied by angiotensin II type 1 receptor downregulation, reduced oxidative stress, and improved endothelial function in patients with stable coronary artery disease

OBJECTIVES: We tested the hypothesis that low-density lipoprotein-cholesterol induces angiotensin II type 1 receptor upregulation that, in turn, accounts for enhanced oxidative stress, and the subsequent endothelial dysfunction in patients with coronary artery disease. METHODS: Brachial artery flow-mediated vasodilation, serum 8-iso-prostaglandin F2alpha (8-isoprostane), and angiotensin II type 1 receptor density on platelets were measured in 19 patients with coronary artery disease, at entry and after 12 weeks of simvastatin therapy, 40 mg/day. RESULTS: At entry there was a significant linear correlation between: angiotensin II type 1 receptor density and plasma low-density lipoprotein-cholesterol; plasma 8-isoprostane and angiotensin II type 1 receptor density; and flow-mediated vasodilation and 8-isoprostane. Simvastatin therapy reduced low-density lipoprotein-cholesterol, downregulated angiotensin II type 1 receptor, decreased 8-isoprostane, and improved flow-mediated vasodilation. The slopes of the presimvastatin and the postsimvastatin angiotensin II type 1 receptor/low-density lipoprotein relationships did not significantly differ, indicating that simvastatin caused a downregulation of angiotensin II type 1 receptor that could be predicted by the low-density lipoprotein reduction. In addition, simvastatin-mediated changes in 8-isoprostane could be predicted by angiotensin II type 1 receptor downregulation, and flow-mediated vasodilation improvement by changes in 8-isoprostane. A significant correlation existed between simvastatin-mediated changes in 8-isoprostane and angiotensin II type 1 receptor. CONCLUSION: The results of this study are consistent with the hypothesis that in coronary artery disease, the impairment of endothelial function is strongly associated with oxidative stress, oxidative stress with cellular angiotensin II type 1 receptor density, and the angiotensin II type 1 receptor density with low-density lipoprotein-cholesterol, suggesting cause-effect relationships between these variables. In support for this notion, these baseline associations were not significantly disturbed by low-density lipoprotein-lowering therapy with simvastatin.