血浆纤维蛋白原和D-二聚体水平与进展性卒中关系的研究

目的探讨缺血性卒中患者血浆纤维蛋白原(Fib)、D二-聚体(D-dimer)水平的动态变化,揭示其在卒中进展中的作用及早期诊断价值。方法用酶联免疫吸附试验(ELISA)法、全自动血凝仪分别检测50例完全性缺血性卒中、40例进展性卒中患者发病24h内、第3天、第7天、第14天、第21天及40例正常对照者血浆D-dime、rFib水平,并对缺血性卒中组患者相应的神经功能缺损情况进行斯堪地那维亚量表(SSS)评分。结果完全性卒中组发病24h内血浆F ib水平显著高于正常对照组,差异有统计学意义(P<0.01),第3天时有下降趋势,第7天时降至正常。进展性卒中组发病24h内血浆Fib水平较完全性卒中组升高更明显(P<0.01),3d时达最高峰,14d降至正常。完全性卒中组发病24h内血浆D-dim er水平较正常对照组明显升高(P<0.01),3d时达高峰,7d降至正常,而进展性卒中组发病24h较完全性卒中组明显升高(P<0.01),至第7天达高峰,第14天迅速降至正常。进展性卒中组3w时神经功能缺损恢复较完全性卒中组为差(P<0.01)。结论对缺血性卒中患者进行血浆F ib和D-d im er水平的动态监测,有助于...     

急性脑梗死患者血清vWF的动态测定及临床研究

目的 动态观察急性脑梗死(ACI)患者血清血管性假血友病因子(vWF)的表达,并探讨其与神经功能缺损程度及年龄、性别等方面的相关性.方法 应用ELISA动态观察52例ACI患者血清vWF的变化,并与52例健康对照者对比,同时应用NIHSS进行神经功能缺损评分.结果 ACI患者血清vWF在发病后早期显著高于正常对照组(P<0.001).血清水平在发病后1～3d已经升高,5～7d达高峰,之后有所下降,15d后仍明显高于正常对照组.但发病后不同时间对比差异无统计学意义(P>0.05).发病3d内血清vWF浓度与当时及发病后15d临床神经功能缺损评分呈正相关.vWF的峰值浓度与患者的年龄、性别等方面均无相关性.结论 ACI早期存在血管内皮的损伤,vWF可判断发病时的血管内皮损伤状态及近期神经缺损程度.     

血红素加氧酶-1基因多态性与脑梗死的相关性

目的探讨血红素加氧酶-1(HO-1)基因启动子基因多态性与ACI患者遗传易感性的关系及碳氧血红蛋白(COHb)在ACI患者中含量的变化。方法采用聚合酶链反应(PCR)和改良双波长分光光度法分析57例急性ACI患者及55例健康对照者血清中HO-1基因启动子(GT)n重复序列不同基因型频率分布特征及碳氧血红蛋白(COHb)含量与ACI的关系。结果ACI组中的Ⅰ类基因型组(携带S等位基因)显著低于2类基因型组(不携带S等位基因)(43.86%比65.45%,P<0.05),提示Ⅰ类基因型与脑梗死的危险性降低相关。ACI组血浆的COHb水平较对照组COHb水平明显升高(t=16.92,P<0.01),提示脑梗死患者血浆COHb含量较高,差异有统计学意义。结论HO-1基因启动子(GT)n重复序列遗传多态性与脑梗死的遗传易感性有关。ACI患者血浆中CO-Hb含量较正常时升高。     

急性脑梗死患者血浆纤维蛋白原和C反应蛋白水平的改变及其与病情和预后的关系

目的 探讨急性脑梗死(ACI)患者血浆纤维蛋白原(Fib)和C反应蛋白(CRP)水平的改变及其与病情和预后的关系.方法 检测86例脑梗死患者(CI组)、27例腔隙性脑梗死患者(LCI组)和48名健康人(正常对照组)的血浆Fib及CRP含量.在CI患者入院当天和4周时进行临床神经功能缺损程度评分(NDS)评定.结果 CI组和LCI组血浆Fib、CRP水平和异常率明显高于正常对照组(均P＜0.01);NDS重型患者血浆Fib、CRP含量明显高于中型、轻型患者(均P＜0.01);中型患者血浆CRP含量显著高于轻型患者(P＜0.01).血浆Fib和CRP含量异常组患者住院4周时显著进步和进步的比率明显低于正常对照组(均P＜0.01),而无变化和死亡的比率明显高于正常对照组(均P＜0.01).结论 ACI患者血浆Fjb和CRP水平均明显升高,病情重的患者升高更明显;血浆Fib、CRP含量升高的患者预后较差.     

进展性脑梗死患者血浆溶血磷脂酸和酸性磷脂水平的变化及其意义

目的 探讨进展性脑梗死(PCI)患者血浆溶血磷脂酸(LPA)和酸性磷脂(AP)水平的变化及其意义.方法 93例急性脑梗死(ACI)患者,根据发病后48 h内病情变化分为PCI组(35例)和非PCI(NPCI)组(58例).检测两组发病后6 h、24 h、3 d、7 d、14 d、21 d血浆LPA和AP的水平,并与正常对照组(50人)比较.结果 与正常对照组比较,PCI组与NPCI组患者发病6 h～14 d时血浆LPA、AP水平均明显增高(均P<0.01);与NPCI组比较,PCI组患者发病6 h～14 d时血浆LPA、AP水平均明显增高(均P<0.01).结论 ACI患者血浆LPA和AP水平均增高,其中PCI患者血浆LPA、AP水平较NPCI患者更高.血浆LPA、AP水平可提示ACI患者病情进展趋势.     

脑出血患者血浆和脑脊液阿片肽含量的变化及纳络酮的干预作用

目的探讨脑出血患者血浆和脑脊液(CSF)阿片肽———β内啡肽(βEP)、强啡肽A113(DynA113)的含量变化及纳络酮的干预作用。方法将60例脑出血患者随机分为纳络酮组和对照组;两组在脑出血常规治疗的基础上,纳络酮组加用纳络酮3.0mg静脉滴注,每日1次,连用14d。采用放射免疫分析法(RIA)检测两组患者治疗前和治疗7d、14d血浆和CSF中βEP、DynA113的含量,分析脑出血部位及出血量与上述指标变化的关系并与正常组(正常血浆组及正常CSF组)比较;对两组脑出血患者治疗前后格拉斯哥昏迷评分(GCS)和神经功能缺损程度评分(NDS)进行比较。结果(1)脑出血患者血浆和CSF中βEP、DynA113含量与两正常组比较明显增高(均P<0.01);不同出血部位患者的血浆和CSF中βEP、DynA113含量的差异无显著性;脑出血量与血浆和CSF中βEP、DynA113含量呈显著正相关(r=0.663、0.480、0.645、0.380,均P<0.01);(2)治疗后纳络酮组血浆和CSF中βEP、DynA113含量明显低于对照组(P<0.05～0.01);GCS、NDS较对照组明显改善(均P<0.05)。结论脑出血后血浆和CSF中阿片肽含量异常升高;纳络酮治疗能明显降低血浆及CSF中阿片肽含量,显著改善脑出血患者的神经功能缺损。     

阿托伐他汀对急性脑梗死患者血清超敏C反应蛋白及一氧化氮水平的影响

目的研究阿托伐他汀对急性脑梗死(ACI)患者血清超敏C反应蛋白(hs-CRP)及一氧化氮(NO)水平的影响。方法将60例ACI患者随机分为阿托伐他汀组(30例)和常规治疗组(30例)。阿托伐他汀组在常规治疗基础上加用阿托伐他汀20mg,每日1次,连续服用14d。在治疗前后检测血清hs-CRP和NO含量,并进行神经功能缺损程度评分(NDS)评定。结果治疗14d时两组血清hs-CRP水平均较治疗前明显下降(均P<0.01),且阿托伐他汀组较常规治疗组下降明显(P<0.01);两组血清NO水平较治疗前明显升高(均P<0.01),且阿托伐他汀组较常规治疗组升高明显(P<0.05);两组NDS评分较治疗前明显下降(均P<0.01),且阿托伐他汀组较常规治疗组下降明显(P<0.05)。结论阿托伐他汀能明显降低ACI患者血清hs-CRP水平,升高NO水平;有助于ACI患者的神经功能恢复。     

进展性脑梗死患者血清C-反应蛋白、S-100β蛋白水平变化及意义

目的探讨进展性脑梗死(PCI)患者血清C-反应蛋白(CRP)与S-100β蛋白(S-100β)水平的变化及意义。方法100例急性脑梗死(ACI)患者根据发病后7 d内神经功能缺损量表评分(SSS)的变化分为PCI组(38例)和非PCI(NPCI)组(62例)。检测两组发病后第1 d、3 d、7 d、14 d血清CRP与S-100β的水平,并与健康对照组比较。结果与NPCI组比较,PCI组发病后各时间点血清CRP及S-100β水平明显升高(均P<0.01);与健康对照组比较,NPCI组血CRP与S-100β水平在发病第1~7 d明显增高(均P<0.01),14 d恢复正常水平。ACI组血清S-100β与CRP水平呈正相关(r=0.856,P<0.01);PCI组发病第1 d血清CRP和S-100β水平与分别第7 d SSS正相关(r1=0.695,r2=0.731;均P<0.05)。结论ACI患者发病早期血清CRP及S-100β水平增高与其病情及PCI的发生相关。     

血浆脂蛋白相关磷脂酶A2水平对进展性脑梗死的预测价值

目的研究血浆脂蛋白相关磷脂酶A2(Lp-PLA2)水平对进展性脑梗死的预测价值。方法采用双抗体夹心酶联免疫吸附法检测168例急性脑梗死患者和72名正常对照者的血浆Lp-PLA2水平。ACI患者每天进行美国国立卫生研究院卒中量表(NIHSS)评分,发病第3 d NIHSS评分比发病第1 d增加≥2分者为进展性脑梗死(进展性脑梗死组),<2分者为稳定性脑梗死(稳定性脑梗死组)。结果 168例ACI患者中进展性脑梗死40例,稳定性脑梗死128例。ACI组血浆Lp-PLA2水平明显高于正常对照组(P<0.01),进展性脑梗死组明显高于正常对照组及稳定性脑梗死组(均P<0.01);稳定性脑梗死组与正常对照组的差异无统计学意义。结论进展性脑梗死患者发病后血浆Lp-PLA2水平明显升高,其可能为早期预测进展性脑梗死发生的生物学指标。     

依达拉奉对颅脑损伤患者血清胃泌素水平及疗效的影响

目的观察依达拉奉对颅脑损伤患者血清胃泌素水平及疗效的影响。方法60例颅脑损伤患者随机分为依达拉奉组及地塞米松组,并给予相应的治疗。检测治疗后1 d、3 d、5 d、7 d血清胃泌素水平;治疗1个月后依据神经功能缺损程度评分(NDS)及Barthel指数(BI)评价疗效。结果依达拉奉组治疗后第3d血清胃泌素水平开始下降,第5 d、7 d恢复正常;地塞米松组第5 d开始下降,第7 d仍高于正常水平;两组间治疗后3 d、5 d及7 d时血清胃泌素水平差异有统计学意义(P<0.05~0.01)。治疗1个月后依达拉奉组NDS及BI明显优于地塞米松组(均P<0.01);总有效率(83.3%)显著高于地塞米松组(63.3%)(P<0.05)。结论依达拉奉能有效降低颅脑损伤患者血清胃泌素水平,改善神经功能缺损,提高疗效。     

Overexpression of glutathione peroxidase protects immature murine neurons from oxidative stress

Neuronal enzyme systems involved in free radical detoxification are developmentally regulated such that intracellular glutathione peroxidase (GPx-1) activity is low in the newborn mouse brain. We hypothesized that neurons expressing a higher level of GPx-1 will be more resistant to hydrogen peroxide (H(2)O(2)) exposure. We show a dose-dependent protection against H(2)O(2) in primary neuronal cultures from fetuses overexpressing human GPx-1 compared to wild types of the same genetic background. Exogenous antioxidants completely protected neurons, even at extremely high H(2)O(2 )concentrations and regardless of the genotype. Specific depletion of glutathione with buthionine sulfoximine increased cell death in transgenic cultures exposed to 200 microM H(2)O(2), reducing protection afforded by increased GPx-1 activity. Increased GPx-1 expression in immature cortical neurons confers protection from oxidative stress, but availability of reducing equivalents determines susceptibility to oxidative cell death.     

GPX3启动子rs8177404、rs8177406、rs8177412基因多态性与脑梗死的相关性研究

目的 探讨血浆谷胱甘肽过氧化酶(Plasma Glutathione Peroxidase,GPX3)启动子rs8177404、rs8177406、m8177412位点基因多态性与脑梗死的相关性.方法 运用聚合酶链反应-连接酶检测方法(PCR-LDR)对94例脑梗死患者和80例健康对照者进行GPX3启动子基因多态性分析.结果 脑梗死组患者中rs8177404、rs8177406、rs8177412位点同时携带C等位基因高于对照组(P<0.05).经多项非条件logistic回归分析提示GPX-3启动子rs8177404、rs8177406、rs8177412同时携带C等位基因成为脑梗死的独立危险因素.结论 GPX3启动子rs8177404、rs8177406、rs8177412基因多态性与脑梗死的发生有一定的关系,可能是脑梗死的一个重要危险因素.     

Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies

Progressive myoclonic epilepsies (EPM) are difficult to treat and refractory to most antiepileptic drugs. Besides epilepsy, EPMs also involve continuous neurological deterioration. Oxidative stress is thought to be an important factor in this process. We therefore analyzed a series of antioxidant enzymes in the blood of patients and compared with healthy age matched controls. In addition patients were given high doses of N-acetylcysteine (NAC), a glutathione percursor to determine if symptoms of EPM would improve. Five patients, four with EPM 1 (Unverricht-Lundborg disease) and one patient with EPM2 (Lafora body disease) were treated with 6 g/day of NAC. Before treatment, plasma samples were analyzed for glutathione peroxidase activity, catalase activity, extracellular superoxide dismutase (SOD) and CuZn-SOD and compared with the controls. Erythrocyte CuZn-SOD was significantly lower in the EPM patients compared to controls. NAC improved markedly and stabilized the neurological symptoms in patients with EPM 1 but had a doubtful effect in the patient with EPM 2.     

Erythrocyte glutathione peroxidase activity and plasma selenium concentration are reduced in maple syrup urine disease patients during treatment

Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex activity. In the present study we evaluated selenium levels in plasma from MSUD patients at diagnosis and under treatment and the activities of glutathione peroxidase, catalase and superoxide dismutase in erythrocytes from treated patients. We verified that MSUD patients present a significant selenium deficiency at diagnosis, which becomes more pronounced during treatment, as well as a decrease of erythrocyte glutathione peroxidase activity during treatment. In contrast, erythrocyte catalase and superoxide dismutase activities were not altered in these patients. Our present results suggest that the reduction of an important antioxidant enzyme activity may be partially involved in the pathomechanisms of this disorder and that plasma selenium levels must be corrected through dietary supplementation in MSUD patients.     

Superoxide dismutases, glutathione peroxidase, and catalase in neuromuscular disease

Studies in experimental muscular dystrophy indicate a possible role for anomalous redox metabolism in the genesis of these disorders, prompting a retrospective review of changes in redox-active enzymes in Duchenne muscular dystrophy (DMD). Both manganous and copper-zinc superoxide dismutase (Mn and CuZn SOD) content and glutathione peroxidase and catalase activities were measured in muscle biopsy specimens taken from normal individuals and from patients with Duchenne muscular dystrophy and other neuromuscular diseases. Muscle from patients with Duchenne dystrophy differed from the norm in that both Mn SOD and CuZn SOD were decreased and glutathione peroxidase was increased. This profile differed from that in anterior horn cell diseases in that CuZn SOD was not decreased in these disorders and from polymyositis, where CuZn SOD was decreased without an increase in glutathione peroxidase. Thus, there appears to be disease-specific changes in these enzymes in DMD. These data support the concept that changes in redox-active enzymes may be associated with the genesis of DMD.     

Brain glutathione peroxidase in neurodegenerative disorders

Glutathione peroxidase is an enzyme that couples the oxidation of reduced glutathione to the detoxification of peroxides. Alterations in the activity of this component of the glutathione oxygen scavenging system in brain have been reported in several conditions associated with oxidative challenge and/or cellular damage. We measured the activity of glutathione peroxidase in autopsied brain regions of neurologically normal adults and in brain of patients with primary degenerative disorder Alzheimer’s type (AD/SDAT), as well as two other neurodegenerative disorders, namely Huntington’s disease and striatonigral degeneration. No significant alterations in enzyme activity were observed in morphologically normal or abnormal brain regions. Our results suggest that in the three brain disorders studied, the neuronal cell loss is unlikely to result from reduced activity of brain glutathione peroxidase, and that a significant compensatory increase in this brain enzyme, consequent to the degenerative processes, does not occur.     

Human plasma glutathione peroxidase and symptom severity in schizophrenia.

BACKGROUND: Previous studies have shown impaired antioxidant defense system in schizophrenia, including alterations in glutathione peroxidase (GSH-Px) activity in erythrocytes. There exists a related enzyme, human plasma GSH-Px (hpGSH-Px), that has not been previously examined in schizophrenia. METHODS: An enzyme-linked immunoassay was used to determine hpGSH-Px levels in male schizophrenic patients (n = 39), using a within-subject, on-off haloperidol (HD) treatment design, compared with age- and gender-matched normal control subjects (n = 37). RESULTS: hpGSH-Px was not significantly different between normal control subjects and patients, consistent with our previous findings in erythrocyte GSH-Px. There were no significant treatment effects. hpGSH-Px was significantly and positively correlated with psychosis rating scores in patients both on and off HD treatment. CONCLUSIONS: Although not different from normal controls, hpGSH-Px levels in patients may reflect oxidative stress associated with greater psychosis severity. The present findings thus suggest that schizophrenic patients, without obvious increase of endogenous antioxidant enzymes (e.g., hpGSH-Px), may be at risk for oxidative damage.     

Higher fat and carbohydrate intake in dementia patients is associated with increased blood glutathione peroxidase activity

BACKGROUND: Mounting evidence implicates diets high in fats and processed sugars with increased generation of free radicals in animals. It is still not clearly established whether such a diet alters antioxidant balance in dementia patients, where an oxidative stress status may already exist. The disruption to lipid metabolism by oxidative stress has been recently linked to neurodegeneration and clinical disease. The aim of this study is to assess the relationship between fat, sugar, carbohydrate and caloric intake levels, and antioxidant status in patients with mild to moderate dementia. METHODS: The levels of 3 essential endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase) were measured in the blood of 26 dementia subjects and 26 cognitively unimpaired controls. Concurrently, the intake levels of relevant nutrients and dietary antioxidants were assessed in all subjects. RESULTS: A statistically significant positive association was observed in the dementia group between glutathione peroxidase activity and the intake of fats (r = 0.44; p = 0.023), carbohydrates (r = 0.46; p = 0.018), total sugars (r = 0.51; p = 0.007) and calories (r = 0.47; p = 0.14). The only significant association in the control group was observed between glutathione peroxidase and fat (r = 0.47; p = 0.015). CONCLUSION: The higher glutathione peroxidase activity among subjects with greater intake of fats, carbohydrates and sugars may represent a compensatory response to the additional increase in oxidative stress in dementia. Our data shed light on the influence of dietary intake on the oxidant-antioxidant system in mild to moderate dementia patients.     

Leucocyte glutathione peroxidase activity and selenium level in multiple sclerosis

In continuation of our previous studies, which demonstrated a decreased glutathione peroxidase (GSH-Px) activity of erythrocytes from multiple sclerosis (MS) patients the activity of some enzymes regulating the peroxide level (GSH-PX and glutathione reductase (GSSG-Rd)) in leucocytes and erythrocytes respectively, the selenium level of whole blood and the β-glucuronidase activity of serum (marker of lysosomal membrane damage) were assayed in this group of patients.GSH-Px activity in lymphocytes and granulocytes from MS patients was significantly (2α ? 0.01) decreased by 35–50%.Erythrocyte glutathione reductase activity was only insignificantly decreased in MS patients. Erythrocyte GSH-Px: GSSG-Rd ratio was 11.0 for the control group, but 8.0 for the MS group.The selenium content of whole blood and serum from Danish MS patients was normal. The selenium level in erythrocytes from Danish MS patients was however higher than the selenium level in erythrocytes from controls.     

Serum selenium concentration, glutathione peroxidase activity and lipid peroxides in a co-twin control study on multiple sclerosis

Serum selenium concentration, glutathione peroxidase activity and lipid peroxides were determined in patients with multiple sclerosis (MS). The series consisted of 13 same-sexed twin pairs derived from the Finnish Twin Cohort of 15,815 pairs. Fourteen subjects had a definite and 1 a probable MS, and their 11 co-twins showed no evidence of central nervous system disease. No statistical differences were observed, but the 3 patients with active progressive MS had a higher mean level of lipid peroxides than the rest of the patients. We suggest that serum lipid peroxidation may be involved in the activity of MS.