Long-term erythropoietin therapy does not affect endothelial markers, coagulation activation and oxidative stress in haemodialyzed patients

INTRODUCTION: Although the general improvement caused by recombinant human erythropoietin (rHuEPO) in the correction of uraemic anaemia cannot be questioned, some data suggest that the changes in the haemostasis, endothelial function and oxidative stress (SOX) are induced. The aim of the present study was to investigate the effect of one-year rHuEPO therapy on the coagulation activation, endothelial injury markers and SOX in haemodialysis (HD) patients. MATERIALS AND METHODS: Assessment of coagulation activation pathway: tissue factor (TF), its inhibitor (TFPI) and prothrombin fragment 1+2 (F1+2); endothelial injury markers: von Willebrand factor antigen (vWF:Ag) and thrombomodulin (TM); and several parameters related to SOX: total peroxide, Cu/Zn superoxide dismutase (Cu/Zn SOD) and autoantibodies to oxidized LDL (OxLDL-Ab) levels were performed in stable HD patients, treated for 12 months with rHuEPO (n=18; mean dose 113.5+/-41 U/kg/week) or not (with Hg<10 g/dl, n=8 and with Hg>10 g/dl, n=12), none of them on iron therapy. RESULTS: Patients with Hg<10 g/dl had a significantly lower erythrocytes count, Ht and Hg levels than those with Hg>10 g/dl and those on rHuEPO therapy. Long-term rHuEPO therapy does not affect coagulation pathway and SOX markers. Treatment with this hormone resulted in a tendency to decrease TM and vWF:Ag concentrations, however these changes did not reach a statistical significance. CONCLUSIONS: These results suggest that one-year rHuEPO therapy seems to exert no additional influence on coagulation activation, endothelial cell damage/activation markers and oxidative stress in patients undergoing regular HD in the absence of concomitant iron supplementation and irrespective from haemoglobin levels.     

Relationship between oxidative stress and extrinsic coagulation pathway in haemodialyzed patients

Enhanced oxidative stress (SOX), endothelial dysfunction and haemostatic abnormalities are common in end-stage renal failure patients undergoing maintenance haemodialysis (HD). We studied associations among circulating immunoreactive total lipid peroxides as a marker of short-time SOX, autoantibodies against oxidized LDL as a surrogate of prolonged SOX, copper/zinc superoxide dismutase (Cu/Zn SOD) as a major antioxidant enzyme, tissue factor (TF) as a principal initiator of extrinsic coagulation pathway counteracted by its inhibitor (TFPI), and prothrombin fragment 1+2 (F 1+2) as a surrogate of activated haemostasis.

Pre-dialysis blood levels of all the markers studied were higher in 24 clinically stable HD patients compared to 11 healthy controls. Spearman's correlations among the three SOX markers were positive but nonsignificant in both HD patients and controls. In HD subjects, increased Cu/Zn SOD levels directly correlated with those of TF (rho=0.551, p=0.005) and TFPI (rho=0.501, p=0.001); the coagulation markers were also positively associated with each other (rho=0.663, p=0.0004). In healthy subjects, the relations between Cu/Zn SOD, TF and TFPI levels were inverse but not significant, and the direct association between TF and TFPI was nonsignificant either.

In conclusion, increased plasma levels of Cu/Zn SOD, the antioxidant enzyme with emerging endothelial cell-protective and antithrombotic properties, may be a novel part of the system counteracting activated extrinsic coagulation system in maintenance HD patients.     

Plasma levels of coagulation and fibrinolysis markers in acute ischemic stroke patients with lone atrial fibrillation

Atrial fibrillation (AF) is a well-defined risk factor for ischemic stroke. Patients with lone AF represent a subgroup of AF patients with the lowest lifelong stroke risk. Nonvalvular atrial fibrillation (NVAF) confers a hypercoagulable state resulting in an increased risk of thromboembolism. This study was performed to determine the contributory role of alteration in the hemostatic markers of thrombin generation and fibrinolysis in patients with lone AF during acute ischemic stroke episode. We studied thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) concentrations in patients with acute middle cerebral artery ischemic stroke due to atherosclerotic large artery disease (n=50), lone AF (n=24) and cardioembolism (n=21). The values were compared with those of age-matched control subjects with lone AF and sinus rhythm (n=21 and 15, respectively). The mean F1+2 concentration was higher in the control subjects with lone AF in comparison with those without AF (p=0.014). Patients with stroke due to possible cardioembolism, from lone AF or other causes, had higher TAT (and marginally higher F1+2) concentrations than those with atherosclerotic stroke (p<0.001). tPA concentrations were not different among groups (p=0.89). PAI-1 levels were marginally higher in stroke patients with lone AF and atherothrombotic large artery disease compared to the controls without AF (p=0.05). These results suggest that in the acute period of ischemic stroke secondary to lone AF, enhancement of the coagulatory activity occurs as a result of increased thrombin generation, similar to other possible sources of cardioembolism. Observed hemostatic alterations in acute ischemic stroke associated with lone AF may indicate some therapeutic and prognostic implications. Received: 3 April 2000 / Accepted in revised form: 20 September 2000     

Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in ₂-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.     

Oxidative stress effects fibrinolytic system in dialysis uraemic patients

INTRODUCTION: Enhanced oxidative stress (SOX) and changes in the fibrinolytic system are common in end-stage renal failure patients undergoing maintenance dialysis. This study attempted to verify the existence of a relationship between SOX documented by Cu/Zn superoxide dismutase (Cu/Zn SOD) and fibrinolysis analyzed by tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) and plasmin/antiplasmin (PAP) complexes in dialysis patients. MATERIALS AND METHODS: Twenty-seven patients on maintenance haemodialysis (HD) and 16 on maintenance peritoneal dialysis (CAPD) were examined together with 18 healthy controls. Pre-dialysis blood levels of all the parameters were determined using commercially ELISA kits. RESULTS: Cu/Zn SOD, uPA and PAP levels were increased in both groups of dialyzed patients compared to the controls. PAI-1 was significantly lower in CAPD subjects compared to HD subjects and control group. PAI-1/uPA ratio and PAI-1/tPA ratio were significantly decreased in CAPD and HD compared to controls, being significantly lower in CAPD patients relative to HD patients. In the patients, increased Cu/Zn SOD levels directly correlated with those of uPA (r=0.565, p<0.0001) and PAP (r=0.335, p<0.05); the fibrinolytic markers were also positively associated with each other (r=0.377, p<0.05). CONCLUSIONS: The positive association between Cu/Zn SOD and both uPA as well as PAP levels suggests a link between SOX and the fibrinolytic activity in dialysis patients. We hypothesize that increased SOX-mediated fibrinolytic activity may be a part of the counter-system against activation of blood coagulation in these patients.     

Activators and inhibitors of coagulation and fibrinolysis in patients with prostatic cancer treated with oestrogen or orchidectomy

The treatment of prostatic cancer with oestrogen has been reported to be associated with cardiovascular side effects. Twenty patients with recently diagnosed prostatic cancer were randomly allocated to oestrogen therapy or orchidectomy. As compared to healthy age matched controls the patients with prostatic cancer had increased base-line levels of fibrinogen (5.2 ± 1.9 g/l versus 3.7 ± 1.0 g/l; p<0.002) and factor VIII:C (166 ± 62% versus 110 ± 29%; p<0.0011).

During oestrogen therapy factor VII increased from 99 ± 22% to 150 ± 47% (p<0.001), while the antithrombin III level fell from 93 ± 10% to 81 ± 13% (p<0.001). Both these changes are in the direction of a hypercoaguable state. Concomitantly plasminogen increased from 113 ± 14% to 142 ± 18% (p<0.001), urokinase inhibiting activity fell from 105 ± 10% to 90 ± 9% (p<0.001) and Cl-esterase inhibitor fell from 110 ± 17% to 86 ±22% (p<0.05) in the oestrogen therapy group. After orchidectomy there were no changes in the activators and inhibitors of coagulation and fibrinolysis studied as compared to baseline values. Furthermore the D dimer, a specific degradation product of crosslinked fibrin increased from a normal to a pathological value in 4 out of 8 tested patients after 6 weeks of oestrogen therapy, but in none out of 9 tested patients in the orchidectomy group.

Briefly stated, patients with prostatic cancer treated with oestrogen have increased levels of factor VII, factor VIII:C and fibrinogen and a decreased level of antithrombin III. All these changes imply a hypercoaguable state, which to some degree seems to be balanced by a compensatory activation of the fibrinolytic system.     

Urokinase-type plasminogen activator and metalloproteinase-2 are independently related to the carotid atherosclerosis in haemodialysis patients

INTRODUCTION: Matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs) system, and fibrinolytic system, have been implicated as important factors in atherosclerosis and vascular remodeling. However, no data are yet available on the associations between these two systems in relation to carotid atherosclerosis in hemodialysis (HD) patients. MATERIAL AND METHODS: We compared plasma levels of MMP-2, MMP-9, TIMP-1, TIMP-2; the parameters of fibrinolytic system: tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPAR) and its soluble receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1), plasmin-alpha2-antiplasmin (PAP) complexes; high sensitivity C-reactive protein (hs CRP) as a marker of inflammation and a surrogate of atherosclerotic disease-intima media thickness (IMT) in HD patients and in healthy controls. RESULTS: The values of the uPA, suPAR, PAP, MMP-2, TIMPs, hs CRP and IMT in the patients significantly exceeded those in controls. The concentrations of MMP-9, tPA and PAI-1 were similar in both investigated groups. uPA, uPAR and PAP were positively associated with MMP-2/TIMPs system; all mentioned above parameters (except TIMP-2) and hsCRP were associated with IMT. Multivariate analysis showed that uPA, MMP-2 and age were the strong independent variables linked to IMT values in HD patients. CONCLUSIONS: The patients on haemodialysis treatment have evidence of disordered fibrinolysis/proteolysis balance in the plasma, independently associated with IMT on multivariate analysis. These data suggest the importance of uPA and MMP-2 levels in the developing of atherosclerosis in these patients.     

A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: Implications for the pathogenesis of acute coronary syndromes

Physical activity and psychological stress are two potential triggers for the onset of acute coronary syndromes (ACS). To examine the mechanisms underlying this association, we systematically reviewed the literature to determine the effects of acute psychological stress and physical activity on haemorheology and haemostasis. Studies examining the haemorheological and haemostatic response to an acute bout of physical activity (i.e. < 60 min) or laboratory psychological stress task were eligible for inclusion. The experimental evidence, although compromised by various methodological weaknesses, suggests that low and moderate intensity physical activity may be cardio-protective through beneficial effects on fibrinolytic system. High levels of physical activity, and psychological to a lesser extent, have been consistently associated with robust changes in haemorheology and haemostasis. Such findings imply that such activities may have the potential to trigger the onset of ACS, although in reality this may be limited sedentary individual and/or those with pre-existing vascular disease. In addition, the data also suggest that individuals may be at a greatest risk of stress-induced thrombogenesis in the period immediately following physical activity or psychological stress, rather than during the activity per se. In conclusion, psychological stress and physical activity may act as potential triggers for the onset of ACS via effects on haemostasis and haemorheology.     

Hemodynamic changes and systemic activation of coagulation and fibrinolysis during controlled endotoxemia in pigs

In this study, we have established a pig model that can combine extensive hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for the study of multiple variables related to the hemostatic system. Sixteen healthy young pigs were studied to evaluate the influence of continuous endotoxin infusion on hemodynamic patterns and activation of coagulation and fibrinolysis. The chief aim of the study was to investigate the applicability of analytical methods primarily developed for use with human plasma samples in quantification of factors and reaction products of the porcine coagulation and fibrinolytic systems, and further, to use these methods to study the longitudinal changes in the plasma levels of these hemostatic variables as a consequence of endotoxin infusion. We found that acute, controlled endotoxemia induced a hemodynamic state of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase in peripheral blood mononuclear cell tissue factor activity was demonstrated, and increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin-antithrombin complexes increased in plasma to maximum levels after 3 hours, accompanied by an ethanol gelation test that was regularly positive after 1 to 2 hours, and fibrin monomer levels that gradually increased maximally 3.8-fold after 6 hours. These changes were followed by gradual decreases of both fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold increase), whereas the peak of plasminogen activator inhibitor-1 activity (14-fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator and completely extinguished plasma tissue plasminogen activator activity. The sequential activation of coagulation and fibrinolysis established a procoagulant state favoring disseminated intravascular coagulation and microthrombus formation, potentially leading to multiple organ dysfunction.     

The roles of BDNF,S100B,and oxidative stress in interferon-induced depression and the effect of antidepressant treatment in patients with chronic viral hepatitis: A prospective study

Objective

The aim of the study was to research the relationship between interferon (IFN) induced depression and sociodemographic characteristics, neurotrophic factors and oxidative stress.

Methods

Sixty four cases, 34 with Chronic Hepatitis B (CHB) and 30 with Chronic Hepatitis C (CHC), were included in the study. The patients were assessed with Structured Clinical Interview for DSM-IV (SCID-I), Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating Scale (HDRS) at baseline on the 2nd and 6th weeks of treatment. S100 calcium binding protein B (S100B), brain-derived neurotrophic factor (BDNF), total antioxidant status (TAS) and total oxidative stress (TOS) levels were measured at the same visits.

Results

In total, 20 patients were diagnosed with major depression (MD) on the sixth week. A significant relationship was found between depression developed after IFN therapy and baseline HARS scores and the type of IFN-α. When the pretreatment levels of HDRS, HARS, S100B, BDNF, TAS, and TOS were compared to those after treatment on the 2nd week, there was a significant increase in HDRS and HARS levels and a significant decrease in the levels of S100B and BDNF. No significant change was determined for TAS and TOS levels.

Conclusions

Our study suggests that the pathogenesis of IFN induced depression may involve neurotrophic factors.     

慢性脑缺血大鼠海马PARP、MDA的表达及阿魏酸钠的抗氧化作用

目的研究慢性脑缺血大鼠海马聚腺苷二磷酸核糖聚合酶(PARP)的表达,并探讨阿魏酸钠在慢性脑缺血所致的氧化应激性损伤中的作用。方法28只成年大鼠用于实验,10只采用双侧颈总动脉结扎制备大鼠慢性脑缺血模型,10只在颈总动脉结扎后给立即予阿魏酸钠腹腔注射,另8只为假手术组。2月后取大鼠海马,采用硫代巴比妥酸法检测丙二醛(MDA)含量,用免疫印迹的方法检测PARP蛋白的表达量。结果慢性脑缺血大鼠海马MDA及PARP蛋白含量明显增多,而经阿魏酸钠治疗后,MDA含量下降,PARP表达下调。结论慢性脑缺血可诱导内源性氧化应激使自由基增多,产生脂质过氧化损伤作用,并导致DNA链的断裂,激活PARP的表达;阿魏酸钠可减少MDA和PARP的生成,在慢性脑缺血氧化应激中起保护作用。     

帕金森病患者体内氧化压力的定量分析

目的 测定帕金森病(PD)患者尿中8-异前列腺素F2α(8-iso-PGF2α)和血中低密度脂蛋白体外氧化延迟时间的变化. 方法 运用病例一对照观察,根据Caine标准选取31例男性PD患者,同时选取31例年龄、影响因素等相当的健康男性为对照.通过铜氧化共轭双烯法在波长234nm测定血中低密度脂蛋白体外氧化延迟时间以及酶联免疫法测定尿中8-iso-PGF2α浓度. 结果 PD患者组尿中8-iso-PGF2α含量比对照组明显增高[(81.1±1.6)ng/mmol肌酐vs(46.9±1.1)ng/mmol肌酐],差异有统计学意义(P<0.05);而血中低密度脂蛋白体外氧化延迟时间明显减低[(63.5±6.0)minvs(84.4±8.8)min],差异有统计学意义(P<0.05). 结论 增高的氧化压力与降低的抗氧化能力在PD的病理过程中具有一定的作用.提示有效的抗氧化治疗可能对控制疾病的发展具有一定的意义.     

Impulsiveness in chronic hepatitis C patients

Objective

The objective was to investigate impulsiveness among chronic hepatitis C (CHC) patients and its association with sociodemographic, clinical and psychopathological factors.

Method

Ninety-one CHC individuals were enrolled in a cross-sectional study at a Brazilian public university-based outpatient’s service for infectious diseases. They were assessed using the Barrat Impulsiveness Scale, Brief Fatigue Inventory, Beck Depression Inventory and Hamilton Anxiety Scale. Structured psychiatric interview was performed according to the Mini International Neuropsychiatric Interview. Multivariate analysis was performed according to linear stepwise forward regression.

Results

The total score of impulsiveness according to BIS in studied population was 64.6±9.8. The scores for the nonplanning, cognitive–attentional and motor domains were 23.8±5, 19.4±2.9 and 21.4±5, respectively. Impulsiveness was associated with lower educational level, current interferon-α (IFN) use, attention-deficit/hyperactivity disorder, alcohol use disorder, mixed anxiety and depressive disorder, specific phobia, bipolar spectrum disorders and anxiety symptoms. During IFN treatment, impulsiveness was also associated with suicide risk.

Conclusion

Impulsiveness was frequent in CHC patients and was associated with several psychopathological alterations. Impulsiveness management should be considered when attending CHC patients.     

Effects of previous physical exercise to chronic stress on long-term aversive memory and oxidative stress in amygdala and hippocampus of rats

Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na⁺, K⁺-ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised + stressed). The animals were subjected to controlled exercise treadmill for 20 min,three times a week, for two months prior to submission to the CVS (40 days). Results show that CVS impaired performance in inhibitory avoidance at 24 h and 7 days after training session. CVS induced oxidative stress, increasing reactive species, lipoperoxidation and protein damage, and decreasing the activity of antioxidant enzymes. The activity of Na⁺, K⁺-ATPase was decreased, but the immunocontents and gene expression of catalytic subunits were not altered. The previous physical exercise was able to improve performance in inhibitory avoidance at 24 h after training; additionally, exercise prevented oxidative damage, but was unable to reverse completely the changes observed on the enzymatic activities. Our findings suggest that physical exercise during the developmental period may protect against aversive memory impairment and brain oxidative damage caused by chronic stress exposure later in life.     

Chronic ethanol exposure causes mitochondrial dysfunction and oxidative stress in immature central nervous system neurons

Cerebellar hypoplasia in experimental fetal alcohol syndrome (FAS) is associated with impaired insulin-stimulated survival signaling. In vitro studies demonstrated that ethanol inhibition of neuronal survival is mediated by apoptosis and mitochondrial dysfunction. Since insulin and insulin-like growth factors (IGFs) regulate energy metabolism, and ethanol can exert its toxic effects by causing oxidative damage to DNA and proteins, we further characterized the effects of chronic gestational exposure to ethanol on mitochondrial gene expression, and the degree to which ethanol inhibition of mitochondrial function is mediated by impaired insulin/IGF responsiveness. Pregnant Long-Evans rats were fed isocaloric liquid diets containing 0, 2, 4.5, 6.5, or 9.25% v/v ethanol from gestation day 6 through delivery. Cerebella harvested on postnatal day 1 were examined for indices of oxidative stress, and mRNA levels of mitochondrial, pro-oxidant, and pro-apoptosis gene expression. Rat primary cerebellar neuron cultures were used to characterize the effects of ethanol (50 mM for 96 h) on insulin and IGF stimulated mitochondrial function and ATP production. Ethanol-exposed cerebella had significantly reduced mRNA levels of mitochondrial genes encoding Complexes II-A, IV, and V, increased expression of p53 and NADPH oxidase (NOX) 1 and 3, and increased immunoreactivity for 4-hydroxy-2,3-nonenal (HNE) and 8-OHdG in cerebellar granule cells. The activations of p53 and NOX genes were highest in cerebella from pups exposed to the 6.5 or 9.25% ethanol containing diet, whereas the impairments in mitochondrial Complex IV and V expression were similar at low and high levels of ethanol exposure. In vitro experiments confirmed that ethanol treatment reduces neuronal expression of mitochondrial genes encoding Complexes IV and V, impairs mitochondrial function and ATP production, and increases HNE and 8-OHdG immunoreactivity, but they also showed that these effects were not insulin- or IGF-dependent. Together, the results suggest that mitochondrial dysfunction, oxidative stress, and DNA damage in FAS may be largely due to the toxic effects of ethanol rather than specific impairments in insulin or IGF signaling.     

儿童细菌性脑膜炎与病毒性脑炎氧化应激水平的变化及意义

目的观察儿童细菌性脑膜炎与病毒性脑炎氧化应激水平的变化。方法选取病毒性脑炎患儿20例,细菌性脑膜炎20例,细菌性脑膜炎患儿按临床评分分为重症组及轻症组。选取20例无中枢神经系统感染儿童为对照组。于治疗前及治疗10 d后测定脑脊液丙二醛(MDA)及超氧化物歧化酶(SOD)水平。结果治疗前细菌性脑膜炎患儿脑脊液中SOD水平明显低于对照组与病毒性脑炎患儿,治疗后SOD水平较治疗前增加,但仍低于对照组,且SOD水平与疾病严重程度相关,重症患儿SOD水平较轻症患儿降低。细菌性脑膜炎患儿脑脊液中MDA水平明显高于对照组与病毒性脑炎患儿,治疗后MDA水平较治疗前降低,但仍高于对照组,且MDA水平与疾病严重程度相关,重症患儿MDA水平较轻症患儿增高。病毒性脑炎患儿脑脊液SOD、MDA水平与对照组比较,差异无统计学意义(P>0.05)。结论细菌性脑膜炎患儿存在氧化应激,脑脊液SOD与MDA水平有助于细菌性脑膜炎的早期诊断及病情严重程度的判定。     

HIV-dementia, Tat-induced oxidative stress, and antioxidant therapeutic considerations

Oxidative stress is thought to play a role in the onset of dementia. HIV-dementia has recently been demonstrated to be associated with oxidative stress as indexed by increased protein and lipid peroxidation in the brain and cerebrospinal fluid compared to HIV non-demented patients. The HIV protein Tat induces neurotoxicity, and, more recently, Tat was found to induce oxidative stress directly and indirectly. The role of Tat in HIV-dementia and possible therapeutic strategies involving endogenous and exogenous antioxidants are discussed.     

氧化应激在慢性缺血性脑白质损伤中的作用

目的 阐明氧化应激是否参与大鼠慢性脑缺血所致的脑白质损伤.方法 健康雄性Wistar大鼠按照完全随机数字表法分为假手术组,持久性双侧颈总动脉结扎3 d组、7 d组、3周组及6周组,每组6只.应用大鼠双侧颈总动脉结扎制备慢性脑缺血模型,检测大鼠脑白质内超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、谷胱甘肽(GSH)含量以及脂质过氧化产物丙二醛(MDA)和4-羟基壬烯醛(4-HNE)加合物的变化.结果 与假手术组比较,慢性脑缺血大鼠脑白质内MDA含量在手术后3周明显增加,手术后6周进一步增高,差异有统计学意义(P<0.05).手术后3d至6周,慢性脑缺血大鼠脑白质内4-HNE蛋白加合物逐渐增高,与假手术组比较有差异有统计学意K(P<0.05).SOD活性在手术后3周和6周才明显降低,与假手术组比较差异有统计学意义(P<0.05).此外,慢性脑缺血大鼠脑白质内GSH含量在手术后7d即开始降低,而在手术后3周及6周则进一步下降,与假手术组比较差异有统计学意义(P<0.05).结论 慢性脑缺血导致大鼠脑白质氧化性损伤增加,抗氧化防御能力降低:氧化性损伤的增加和抗氧化防御能力的降低与慢性脑缺血所致的脑白质损伤密切相关.