动脉粥样硬化的氧化应激生物标记物研究进展

越来越多的证据表明,氧化应激在动脉粥样硬化(AS)性心血管疾病形成中的重要作用。最近的一些病理学方面的研究也发现,某些特异性的调节物参与了这些氧化应激反应并可促进AS斑块在血管壁的形成和破裂。这些特异性的调节物能在人体内测出并作为AS性心血管疾病风险评估的生物标记物,本文就这些生物标记物作一综述。     

Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects

The disturbances in pro- and antioxidant balance may play an important role in the pathomechanism of aging. The pineal hormone melatonin, which exerts effective antioxidative properties, is suggested to be involved in the aging process. The aim of this study was to compare the oxidative stress in erythrocytes of healthy young adults and elderly people, and to determine the influence of melatonin supplementation on measured parameters in both examined groups. The malondialdehyde (MDA) and reduced glutathione levels as well as Cu-Zn superoxide dismutase (SOD-1), catalase, glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR) activities in erythrocytes and morning serum melatonin concentration in 14 healthy young adults and 14 healthy elderly people at baseline and after the 30th day of melatonin (5 mg daily) supplementation were determined. A significant age effect on increasing the MDA level and decreasing SOD-1, GSH-Px and GR activities as well as melatonin concentration was observed. Melatonin supplementation resulted in a significant increase in melatonin concentration, SOD-1 and GR activities and a decrease in the MDA level in both examined groups. These data indicate an age-related augmentation of oxidative stress in erythrocytes and the improvement of erythrocytic antioxidative defense by melatonin administration. These results might suggest melatonin supplementation to prevent age-related diseases and to prolong the lifespan and improve the quality of life of elderly people.     

Effect of vitamin E and selenium supplementation on oxidative stress status in pulmonary tuberculosis patients

Background and objective:   Increased production of reactive oxygen species secondary to phagocyte respiratory burst occurs in pulmonary tuberculosis (TB). The present study evaluated the efficacy of vitamin E–selenium supplementation on oxidative stress in newly diagnosed patients treated for pulmonary TB.
Methods:   A double-blind, placebo-controlled trial including patients with newly diagnosed TB was conducted. The intervention group ( n  = 17) received vitamin E and selenium (vitamin E: 140 mg α-tocopherol and selenium: 200 μg) and the control group ( n  = 18) received placebo. Both groups received standard anti-TB treatment. Assessment of micronutrient levels, oxidative markers and total antioxidant capacity were carried out at baseline and 2 months after the intervention.
Results:   Malondialdehyde levels were significantly reduced in the intervention group ( P  = 0.01), while there was minimal reduction in the control group. The mean plasma level of total antioxidants was increased significantly ( P  = 0.001) in both the intervention and the control groups.
Conclusion:   A 2-month intervention with vitamin E and selenium supplementation reduces oxidative stress and enhances total antioxidant status in patients with pulmonary TB treated with standard chemotherapy.     

Melatonin reduces oxidative stress in erythrocytes and plasma of senescence-accelerated mice

It has been suggested that oxidative stress is a feature of aging. The goal of the present study was to assess the oxidant effects related to aging and the protective role of exogenous melatonin in senescence-accelerated mice (SAMP8). Two groups of SAMP8 mice (males and females) were compared with their respective control groups of SAMR1 mice (senescence-resistant inbred strain) to determine their oxidative status without melatonin treatment. Four other groups of the same characteristics were treated with melatonin (10 mg/kg/day) in their drinking water. The melatonin concentration in the feeding bottles was titrated according to water consumption and body weight (i.e. 0.06 mg/mL for 30 g of body weight and 5 mL/day of water consumption). The treatment began when animals were 1-month old and continued for 9 months. When mice were 10-month old, they were anesthetized and blood was obtained. Plasma and erythrocytes were processed to examine oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), and hemolysis. The results showed greater oxidative stress in SAMP8 than in SAMR1, largely because of a decrease in GSH levels and to an increase in GSSG and TBARS with the subsequent induction of the antioxidant enzymes GPX and GR. Melatonin, as an antioxidant molecule, improved the glutathione-related parameters, prevented the induction of GPX in senescent groups, and promoted a decrease in SOD and TBARS in almost all the groups.     

Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention

With an increasing prevalence, pediatric obesity is often a prelude to adulthood obesity, and represents a major public health issue. Comorbidities are very common and severe in obese adults, justifying the search for earlier markers or risk factors for cardiovascular diseases in obese children. Endothelial dysfunction has been found to be present in the early stages of atherosclerosis, and can be non-invasively assessed with widely accepted and well-standardized techniques at the macrocirculation level. Endothelial dysfunction at the microcirculation level is less documented in obese children. Obesity in children has been repeatedly and independently correlated to endothelial dysfunction, inflammation and oxidative stress markers, although the relationship between these factors remains to be investigated. However, this would not only allow substantial improvements in risk stratification, but also provide essential data regarding the evolution of endothelial dysfunction in childhood obesity, especially during puberty when pro-inflammatory and pro-oxidative changes, with relative insulin resistance, occur. Therapeutic strategies such as lifestyle interventions in early childhood obesity appear all the more necessary, optimally including both exercise and diet because of their known effects on inflammatory and oxidative stress markers, potentially reversing endothelial dysfunction.     

Comparison of oxidative stress biomarkers in hypertensive patients with or without hyperhomocysteinemia

Hyperhomocysteinemia is an independent risk factor for cardiovascular impairment in hypertension. Oxidative stress is important in the molecular mechanisms associated with hypertension, but there are few studies focusing on the comparison of oxidative stress biomarkers in hypertensive patients with or without hyperhomocysteinemia. The study included 50 newly diagnosed hypertensive patients with hyperhomocysteinemia, 50 newly diagnosed hypertensive patients without hyperhomocysteinemia, and 50 age-matched healthy controls. Serum levels of malondialdehyde, nitric oxide, 8-isoprostane-F2_ɑ, superoxide dismutase, catalase, and glutathione peroxides were compared. Levels of malondialdehyde and 8-isoprostane-F2_ɑ were higher in both hypertensive groups than in the control group (8.3 ± 1.8 μmol/L vs. 6.5 ± 1.3 μmol/L vs. 4.3 ± 1.2 μmol/L, P < 0.05; 23.5 ± 12.1 pg/mL vs. 17.4 ± 10.3 pg/mL vs. 13.9 ± 7.5 pg/mL, P < 0.05), while levels of superoxide dismutase and catalase were lower in both hypertensive groups than in the control group (120.5 ± 13.7 U/mL vs. 131.3 ± 18.2 U/mL vs. 149.1 ± 14.6 U/mL, P < 0.05; 23.8 ± 7.4 U/mL vs. 24.6 ± 9.2 U/mL vs. 33.5 ± 8.2 U/mL, P < 0.05). In hypertensive subgroups, serum malondialdehyde levels were higher in the hyperhomocysteinemia group than the other group (8.3 ± 1.8 μmol/L vs. 6.5 ± 1.3 μmol/L; P < 0.05), and superoxide dismutase activities were lower in the hyperhomocysteinemia group than the other group (120.5 ± 13.7 U/mL vs. 131.3 ± 18.2 U/mL; P < 0.05). Moreover, in hypertensive patients, homocysteine levels were significantly correlated with malondialdehyde (r = 0.39, P < 0.01), 8-isoprostane-F2ɑ (r = 0.47, P < 0.05), superoxide dismutase (r = ?0.51, P < 0.01), and catalase (r = ?0.51, P < 0.05), respectively. Our ?ndings demonstrated oxidative stress was more severe in hypertensive patients with hyperhomocysteinemia than those hypertensive patients without it. Besides, there were strong relationships between homocysteine activities and oxidative/antioxidative parameters, which indicated that homocysteine might aggravate the oxidative stress in hypertension to produce contributory effects on cardiovascular impairment.     

Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients

Abstract: An elevated oxidative status in the aging organism may be involved in the development of non‐insulin dependent diabetes mellitus (NIDDM). Melatonin, a potent antioxidant agent, is essential for glucose homeostasis and regulation. The aim of this study was to determine the influence of melatonin supplementation on the oxidative stress parameters in elderly NIDDM patients. The malondialdehyde (MDA) concentration, Cu‐Zn superoxide dismutase (SOD‐1) activity in erythrocytes, the level of nitrate/nitrite in plasma and morning melatonin concentration and oxidase activity of ceruloplasmin (Cp) in serum in 15 elderly NIDDM patients at baseline and after the 30 days of melatonin supplementation (5 mg daily) in comparison with levels in 15 healthy elderly volunteers were determined. A significant increase of MDA level and decrease of SOD‐1 activity and melatonin concentration were observed in NIDDM patients. Cp oxidase activity and nitrate/nitrite level were similar in both examined groups. Melatonin administration in NIDDM patients resulted in a significant increase in the morning melatonin concentration and SOD‐1 activity, and a reduction in the MDA level and Cp oxidase activity. Statistically significant alterations in nitrate/nitrite levels were not observed. These results indicate an improvement of antioxidative defense after melatonin supplementation in the NIDDM individuals and suggest melatonin supplementation as an additional treatment for the control of diabetic complications.     

Alterations in oxidative stress scavenger system in aging rat brain and lymphocytes

There is a large body of evidence indicating an age-related increase in the rate of mitochondrial O₂ ⁻ and H₂O₂ generation and huge amounts of oxidative damage leading to several neurodegenerative disorders, perhaps due to an imbalance between free radical generation and anti-oxidant defense system. The aim of the present study was to elucidate the effect of aging on free radical scavenger system profile in rat brain and lymphocytes. The enzyme activities of γ-GCS, GR, GPx, γ-GTP, GST, catalase, and SOD as well as GSH content were assayed from discrete brain areas viz., CH, CB,BS and DC along with lymphocytes from four different age group rats, namely, 1-month-oldyoung rats, 3–4-month-old young adults, 12-month-old adults and 24-month-old aged rats. Significant decline was observed in all the enzyme activities in 12- and 24-month-old rats as compared to 3–4-month-old young adult rats and also, 1-month-old rats showed lower levels of enzyme activities as compared to 3–4-month-old rats. The maximum scavenger system activity was found in the young adult rats (3–4 months) as compared to the remaining age groups. Lymphocytes and brain showed a parallel pattern of age-related alterations in the free radical scavenger system components. The analysis of such alterations is important in ultimately determining the basis of neuronal dysfunction associated with aging and also defining the nature of these changes may help to develop therapeutic means to cure not only elderly but also individuals suffering from certain organic or psychiatric disorders. This revised version was published online in July 2006 with corrections to the Cover Date.     

Oxidative stress is associated with greater mortality in older women living in the community

OBJECTIVES: To determine whether oxidative stress, as implied by oxidative damage to proteins, is associated with greater mortality in older women living in the community. DESIGN: Longitudinal. SETTING: Women's Health and Aging Study I, Baltimore, Maryland. PARTICIPANTS: Seven hundred forty-six moderately to severely disabled women, aged 65 and older, with baseline measures of serum protein carbonyls. MEASUREMENTS: Serum protein carbonyls, which consist of chemically stable aldehyde and ketone groups produced on protein side chains when they are oxidized, were measured using enzyme-linked immunosorbent assay. Multivariate logistic regression was used to adjust for potential confounders. RESULTS: During 5 years of follow-up, 202 (27.1%) participants died. Geometric mean serum protein carbonyls were 0.091 nmol/mg in women who died and 0.083 nmol/mg in those who survived (P=.02). Log(e) protein carbonyls (nmol/mg) were associated with greater risk of mortality (hazards ratio=1.34, 95% confidence interval=1.01-1.79, P=.04) in a multivariate Cox proportional hazards model adjusting for age, current smoking, and body mass index. CONCLUSION: Greater oxidative stress, as indicated by elevated serum protein carbonyl concentrations, was associated with greater risk of death in older women living in the community who were moderately to severely disabled. Prevention of oxidative stress may reduce the risk of mortality.     

依布硒啉对急性肺损伤大鼠氧化应激的影响

目的 观察依布硒啉对内毒素性急性肺损伤的保护作用.方法 健康雄性SD大鼠,随机分成6组:正常对照组、模型组、依布硒啉高剂量组、中剂量组、低剂量组和地塞米松对照组.通过尾静脉注射LPS(5 mg/kg)建立模型,治疗组于造模前30 min,大鼠腹腔注射依布硒啉(7.5 mg/kg、15 mg/kg、30 mg/kg),对照组和模型组分别注入等量溶剂.造模后6h,麻醉放血处死动物,并取肺组织,测定肺湿质量/干质量.采用硫代巴比妥酸和黄嘌呤氧化法分别检测肺组织中超氧化物歧化酶SOD活性和丙二醛MDA及髓过氧化物酶(MPO)含量.光镜下观察肺组织病理学改变.结果 依布硒啉治疗组与模型组相比,肺湿质量/干质量降低,肺组织SOD的活性明显增高,MDA和MPO含量显著降低(P＜0.05),病理改善明显.结论 依布硒啉对内毒素性急性肺损伤有一定保护作用,其机制可能与提高抗氧化能力有关.     

老年早期糖尿病性心肌病变患者血糖强化治疗前后氧化应激水平的变化

目的评价老年早期糖尿病性心肌病（DCM）患者胰岛素泵强化治疗前后氧化应激水平的变化。方法对2009年2月至2011年10月确诊的30例老年早期DCM患者采用胰岛素泵强化治疗,治疗达标前后分别测定超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH．PX）、丙二醛（MDA）水平,进行比较。结果胰岛素泵强化治疗后,患者血浆中的SOD[（118．40±25．41）VS（171．16±27．76）U／ml]和GsH-PX[（120．53±46．26）vs（175．58±52．37）u]明显上升（P〈0．01）,MDA明显下降[（49．53±14．42）vs（22．65±12．54）nmol／ml,P〈0．01]。空腹血糖[（5．64±0．53）vs（10．96±2．63）mmol／L]、餐后2小时血糖[（7．74±1．46）vs（18．50±3．24）mmol／L]、胰岛素抵抗指数[（2．50±1．12）vs（5．90±1．82）mmol／L]、总胆固醇[（4．40±0．45）．kS（8．44±0．90）mmol／L]、甘油三酯[（2．80±1．01）vs（6．84±1．83）mmoi／L]、低密度脂蛋白胆固醇[（3．01±0．73）vs（5．11±1．35）mmol／L]、游离脂肪酸[（0．34±0．11）vs（0．73±0．10）mmol／L]明显降低（P〈0．05）,胰岛素分泌功能指数明显上升[（73．32±12．20）vs（11．80±5．50）mmol／L,P〈0．05]。心脏舒张功能（E／A）明显改善[（0．74±0．35）vs（1．09±0．23）,P〈0．01]。结论老年早期DCM患者使用胰岛紊泵强化治疗可明显降低氧化应激水平,改善心脏舒张功能。     

氧化应激调节klotho基因启动子活性的作用研究

目的研究氧化应激对klotho基因启动子活性的影响及抗氧化系统的作用。方法构建klotho基因启动子片段的荧光素酶报告基因重组质粒,将重组质粒和内对照质粒海肾荧光素酶报告质粒以脂质体法共转染Hela细胞,以0、400、600、800和1000μmol/L的过氧化氢处理Hela细胞,依次分为对照组、1组、2组、3组和4组,观察klotho基因启动子的活性变化,并分析总抗氧化能力(T-AOC)、谷胱甘肽过氧化物酶(GSH-PX)和过氧化氢酶(CAT)等抗氧化酶的活性变化对此过程的影响。结果与对照组比较,1组的klotho基因活性无明显改变(P>0.05);2组、3组和4组的klotho基因启动子活性下降(P<0.01),2组、3组和4组T-AOC、CAT和GSH-PX活性明显降低(P<0.05.P<0.01),与2组比较,3组和4组T-AOC和GSH PX活性明显降低(P<0.05)。klotho基因启动子活性下降与T-AOC、CAT和GSH-PX活性下降呈正相关(r=0.805、0.812、0.944,P=0.00)。结论氧化应激下调klotho基因的表达,可能与其下调该基因的启动子活性密切相关,且氧化应激过程中抗氧化酶活性的变化与klotho基因启动子活性的下降可能相关。     

Melatonin‐rich transgenic rice plants exhibit resistance to herbicide‐induced oxidative stress

To examine whether melatonin‐rich plants can defend against oxidative stress, we subjected melatonin‐rich transgenic (MRT) rice plants to the singlet‐oxygen‐generating herbicide butafenacil. Both MRT and transgenic control (TC; expressing the vector only) rice seeds germinated and grew equally well in continuous dark on half‐strength Murashige and Skoog (MS) medium containing 0.1 μm butafenacil. However, after transferring the seedlings to light, the TCs rapidly necrotized, whereas the MRT seedlings showed resistant phenotypes. Seven‐day‐old MRT seedlings treated with 0.1 μm butafenacil were resistant to the herbicide and contained high chlorophyll levels and low malondialdehyde and hydrogen peroxide contents compared with the TCs. As they did before the herbicide treatment, the MRT plants also produced much more melatonin after the herbicide treatment than the TCs. In addition, the MRT plants exhibited higher superoxide dismutase and catalase activities before and after the herbicide treatment compared with the TCs. This is the first report showing that MRT plants exhibit resistance against a peroxidizing herbicide that acts by generating reactive oxygen species (ROS) that kill plants. This result indicates that melatonin scavenges ROS efficiently in vivo in the transgenic plants, leading to oxidative stress resistance.