氧化低密度脂蛋白和一氧化氮的相互作用及其在缺血性及脑卒中 …

目的研究急性缺血性脑卒中患者血浆氧化低浓度脂蛋白与一氧化氮的关系及它们在缺血性脑卒中发病机制中的作用。方法 测定４５名健康体检者，２０例动脉硬化患者和７５例急性缺血性脑卒中患者血浆ＬＤＬ及体外氧化获得的ｏｘＬＸＬ对血小板聚集功能和ＮＯ水平的影响。结果 动脉硬化和脑卒中患者血浆ｏｘＬＤＬ值明显升高，提示血浆ＬＤＬ及ｏｘＬＤＬ对血小板聚集有明显的促进作用，同时降低ＮＯ水平；血小板聚集的增强和ｏｘＬＤＬ     

动脉粥样硬化性血栓性脑梗塞患者血浆氧化修饰低密度蛋白 …

目的 探讨氧化修饰低密度脂蛋白（ＯＸ－ＬＤＬ）与动脉粥样硬化性血栓性脑梗塞（ＡＴＣＩ）发生,发展的关系。方法 应用酶联免疫吸附试验（ＥＬＩＳＡ）双抗夹心法检测了８３例ＡＴＣＩ患者血浆ＯＸ－ＬＤＬ含量变化。结果 （１）ＡＴＣＩ组血浆ＯＸ－ＬＤＬ水平显著高于正常对照组（Ｐ〈０．０１）;血浆ＯＸ－ＬＤＬ水平变化与病程有关,但与梗塞部位无关。（２）ＡＴＣＩ患者血浆ＯＸ－ＬＤＬ水平与血糖、血胆固醇呈正相关。     

动脉粥样硬化性血栓性脑梗塞患者血浆氧化修饰低密度脂蛋白含量的研究

目的探讨氧化修饰低密度脂蛋白（ＯＸ－ＬＤＬ）与动脉粥样硬化性血栓性脑梗塞（ＡＴＣＩ）发生、发展的关系。方法应用酶联免疫吸附试验（ＥＬＩＳＡ）双抗夹心法检测了８３例ＡＴＣＩ患者血浆ＯＸ－ＬＤＬ含量变化。结果（１）ＡＴＣＩ组血浆ＯＸ－ＬＤＬ水平显著高于正常对照组（Ｐ＜０．０１）;血浆ＯＸ－ＬＤＬ水平变化与病程有关,但与梗塞部位无关。（２）ＡＴＣＩ患者血浆ＯＸ－ＬＤＬ水平与血糖、血胆固醇呈正相关。结论ＯＸ－ＬＤＬ可能参与了ＡＴＣＩ的发生和发展过程。     

Ⅱ型糖尿病伴脑梗死病人血浆氧化修饰低密度脂蛋白测定的意义

探讨血浆氧化修饰低密度脂蛋白水平的变化与Ⅱ型糖尿病（ＤＭ）伴脑梗死（ＣＩ）的关系。方法：应用ＥＬＩＳＡ法测定ＤＭ伴ＣＩ病人血浆ＯＸＬＤＬ的水平,另设单纯性ＣＩ组及正常对照组。结果（１）无论是否合并ＤＭ,ＣＩ组病人血浆ＯＸＬＤＬ水平较正常对照组明显增高;且ＤＭ伴ＣＩ组明显高于单纯于ＣＩ组。（２）血浆ＯＸＬＤＬ水平与ＬＤＬ－Ｃ、ａｐｏＢ水平呈正相关,而与ＨＤＬ－Ｃ水平呈负相关。结论：ＯＸＬＤＬ在ＤＭ伴     

脑梗塞患者血清NO、oxLDL测定及临床意义探讨

我们检测５１例脑梗塞患者和３０例对照组血清一氧化氮（ＮＯ）及氧化型低密度脂蛋白（ｏｘＬＤＬ）的水平,探讨其与脑梗塞发病的关系。１对象和方法１．１对象脑梗塞患者５１例,均经ＣＴ或核磁共振扫描确诊,男２７例,女２４例,平均年龄６４．４±８．８２岁;正常对...     

oxLDL,Lp（a）与脑血管疾病的关系

测定５１例脑血管病和２０例对照组的血浆ｏｘＬＤＬ和血清Ｌｐ（ａ）。结果脑血管病组明显高于对照组，脑血管病各分组（脑出血、脑栓塞、蛛网膜下腔出血）的ｏｘＬＤＬ亦高于对照组，脑出血、脑梗塞分组的Ｌｐ（ａ）高于对照组。ｏｘＬＤＬ及Ｌｐ（ａ）异常与患者的性别、年龄、病程及常规血脂检查异常率无相关。结论：ｏｘＬＰＬ、Ｌｐ（ａ）升高与脑血管病发病密切相关，是估价中风危险因素重要的、独立的脂蛋白参数之一。     

过氧化低密度脂蛋白对家兔脑动脉硬化和脂蛋白分子颗粒的影响

为了阐明过氧化低密度脂蛋白（ＯＸ－ＬＤＬ）能否引起家兔体内脑动脉粥样硬化的形成，以及该物质对血浆脂蛋白ＬＤＬ（ＰｌａｓｍａＬｏｗＤｅｎｓｉｔｙＬｉｐｏｐｒｏｔｅｉｎ）脂质生化学和其分子超微结构的影响。分以下３组，即生理盐水对照组、正常ＬＤＬ（Ｎ－ＬＤＬ）组以及脂质过氧化ＬＤＬ（ＯＸ－ＬＤＬ）组，用一定量的上述液体分别注射各自的家兔耳静脉内，每日１次，共５周。发现Ｎ－ＬＤＬ组与对照组，血浆中ＬＰＯ和ＡｐｏＢ的含量以及血浆ＬＤＬ分子颗粒和脑动脉超微结构均未见明显变化，而ＯＸ－ＬＤＬ组不仅血浆中ＬＰＯ和ＡｐｏＢ含量经周逐渐增加，血浆ＬＤＬ分子颗粒也逐渐增大，脑动脉粥样硬化形成也很明显。说明ＯＸ－ＬＤＬ是引起体内脑动脉硬化形成的原因之一。     

脑出血与8项血脂指标的关系探讨

测定了１２５例脑出血病人的血总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、高密度脂蛋白（ＨＤＬ）、低密度脂蛋白（ＬＤＬ）、载脂蛋白Ａ－１、Ｂ－１００（ＡｐｏＡ－１、ＡｐｏＢ－１００）、脂蛋白（ａ）［ＬＰ（ａ）］和氧化修饰低密度脂蛋白（ｏｘＬＤＬ）浓度。结果显示：与对照组比较，ＡｐｏＢ－１００、ｏｘＬＤＬ显著增高，ＨＤＬ、ＡｐｏＡ－１显著降低（Ｐ＜０．０１），ＬＤＬ明显降低（Ｐ＜０．０５），ＴＣ、ＴＧ、ＬＰ（ａ）无明显变化（Ｐ＞０．０５）。提示：血ＬＤＬ、ＡｐｏＢ－１００、ｏｘＬＤＬ浓度增高和ＨＤＬ、ＡｐｏＡ－１浓度降低与脑出血有一定的相关关系，可作为脑出血的危险因素。     

高胆固醇及高糖负荷对于兔脑缺血后血脂和低密度脂蛋白脂质过氧化的影响

测定并观察了４９只高胆固醇食、高糖食和正常食对新西兰白兔脑缺血后血脂、脂质过氧化物（ＬＰＯ）含量的影响，并提取血浆低密度脂蛋白（ＬＤＬ）制成氧化型低密度脂蛋白（ｏｘＬＤＬ），用薄层层析法分析了其脂质成分变化。结果示：胆固醇组血清游离脂肪酸（ＦＦＡ）、朋固醇（ＣＨ）和磷脂（ＰＬ）含量显著增高，且脑缺血后增高更显著（Ｐ均＜０．０１），血浆和ＬＤＬ的ＬＰＯ含量亦显著增高。胆固醇食组ＴＬＣ中Ｘ带（６．４／±２．６％）显著高于正常食组（２．８％±０．８％）和糖水组（１．２％±１．３％），Ｐ均＜０．０１。经Ｃｕ￣（２＋）溶液透析后，ＬＦＦＡ及ＰＬ带增高，而胆固醇酯（ＣＥ）及甘油三酯（ＴＧ）带减少。结果表明，高胆固醇食及脑缺血可导致脂质代谢紊乱，导致较多ＬＰＯ和ｏｘＬＤＬ生成，从而加速动脉粥样硬化和脑卒中。ＴＬＣ中的Ｘ带可作为衡量脂质过氧化物的一个重要指标。     

脑梗死患者OX-LDL、LP(a)、APOE及NO含量测定的临床意义

脑梗死的重要病理基础是动脉粥样硬化 ,研究证实 ,氧化修饰的ＬＤＬ(ＯＸ -ＬＤＬ)与动脉粥样硬化早期病变的发生发展密切相关。ＬＰ(ａ)是心脑血管的独自危险因素。ＡＰＯＥ在胆固醇的转运及脂蛋白的代谢过程中发挥重要作用。ＮＯ是一种细胞内和细胞间的信使分子 ,具有广泛的生物作用 ,参与调节体内各种生理病理活动。我们对 5 2例脑梗死急性病例的ＯＸ -ＬＤＬ、ＡＰＯＥ、ＬＰ(ａ)、ＮＯ的水平进行检测分析。1　资料与方法1 1　资料　 5 2例脑梗死急性病例 (男 3 8例 ,女 14例 )均来自本院住院病人 ,年龄 48± 15 6岁。根据 1986年第二…     

卡托普利上调缺血性脑卒中患者血小板一氧化氮合酶的实验和临床研究

目的　研究卡托普利对缺血性脑卒中患者血小板一氧化氮合酶 (NOS)的上调及临床应用。方法　测定急性缺血性脑卒中患者及健康体检者的血小板NOS及在体外加氧化低密度脂蛋白 (oxLDL)、卡托普利后血小板NOS的活性 ;检测患者服卡托普利前、服后 1个月及 3个月的血浆oxLDL、NOS、一氧化氮 (NO) ,血小板NOS、NO ,同时检查神经功能。结果　 (1)卒中组和对照组血小板加oxLDL后 ,NOS值均明显下降 (P <0 .0 1) ,卒中组下降更明显 ;(2 )两组血小板同时加卡托普利、oxLDL后 ,NOS值均明显升高 (P <0 .0 1) ,卒中组升高更明显 ;(3)两组血小板单纯加卡托普利后 ,其NOS值均明显升高 (P <0 .0 1) ,同样亦是卒中组升高更明显 ;(4 ) 4 0例缺血性脑卒中患者服用卡托普利后血浆oxLDL明显下降 ,血小板NOS、NO ,血浆NOS、NO明显增高 ,神经功能明显改善。结论　卡托普利有直接上调血小板NOS的作用 ,卡托普利通过提高血小板NOS活性的作用 ,可以改善内皮功能 ,防治脑卒中     

Variable platelet response to aspirin in patients with ischemic stroke

BACKGROUND: A large number of patients experience ischemic stroke despite treatment with aspirin (acetylsalicylic acid, ASA). It is not clear whether all of these patients with ischemic stroke respond normally to ASA or are hyporesponsive as assessed by inhibition of aggregation and thromboxane (TX) synthesis. METHODS: We studied the effect of ASA given orally and ASA in vitro on collagen- and arachidonic-acid-induced TX formation and aggregation in platelet-rich plasma of 90 patients with ischemic stroke and 25 healthy control subjects. RESULTS: Thirty-seven patients were being treated with ASA at the time of stroke. Arachidonic-acid-induced TX formation was not depressed below a predefined threshold of 25 ng/ml in 9 patients. Eight of these however exhibited a normal platelet sensitivity to ASA in vitro, suggesting poor compliance or a pharmacokinetic mechanism of nonresponse. The addition of ASA in vitro did not inhibit arachidonic-acid-induced TX formation below the above threshold in 6 patients (11%) in the group of 53 stroke patients not receiving oral ASA, indicating an impaired response to ASA at the platelet level. Moreover, platelets from stroke patients showed an increased collagen-induced, TX-independent aggregation as compared with those of healthy individuals. CONCLUSION: Different categories of ASA nonresponders can be distinguished in patients with ischemic stroke. These include patients with poor bioavailability or noncompliance, an impaired platelet response to ASA in vitro and an increased, TX-independent hyperreactivity to collagen.     

血浆同型半胱氨酸与青年缺血性卒中关系的探讨

目的 探讨血浆同型半胱氨酸（Homocysteine,Hcy）水平与青年缺血性卒中及其不同类别之间的关系.方法 分别测定60例青中年缺血性卒中患者及60例正常健康青中年对照者血浆Hcy水平.结果 全部缺血性卒中患者血浆Hcy水平均高于同龄段健康对照组（P＜0.01）,其中青年缺血性卒中患者血浆Hcy水平又高于中年患者（P＜0.05）,青年缺血性卒中组中以大动脉粥样硬化性卒中的平均Hcy水平为最高,与其他类别组比较差异有意义（P＜0.05）.结论 Hcy是缺血性卒中重要发病原因之一,且Hcy对青年缺血性卒中影响比中年大,尤以大动脉粥样硬化性卒中更甚.     

Antioxidant Effects of Statins in Patients with Atherosclerotic Cerebrovascular Disease

Background and Purpose

Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropic and low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that high-dose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke after statin use. This study evaluated changes in oxidative stress markers after short-term use of a high-dose statin in patients with atherosclerotic stroke.

Methods

Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and 1 month after dosing, and the serum levels of four oxidative stress markers-malondialdehyde (MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2''-deoxyguanosine (8-OHdG)-were evaluated to determine the oxidation of MDA and lipids, proteins, and DNA, respectively, at both of those time points.

Results

The baseline levels and the degrees of reduction after statin use differed among the oxidative stress markers measured. MDA and PCO levels were associated with infarct volumes on diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin use decreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While the reduction in MDA levels after statin use was not associated with changes in cholesterol, that in oxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05).

Conclusions

The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidative stress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidation via lipid-lowering-dependent and -independent mechanisms, but not against protein or DNA oxidation in atherosclerotic stroke patients.     

Dynamics of LDL oxidation in ischemic stroke patients

OBJECTIVE: Oxidative modification of human low density lipoprotein (LDL) plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the oxidative modification of LDL in the group of patients with ischemic stroke. MATERIAL AND METHODS: In the group of 43 patients 3 months after ischemic stroke and in the age and sex-matched control group, the kinetics of LDL oxidation and level of vitamin E were estimated. The susceptibility of LDL to oxidation was evaluated in isolated LDL exposed to in vitro oxidation. In 26 patients, after diet change, clinical and laboratory investigations were repeated 9 months later. RESULTS: In the patient group, susceptibility of LDL to oxidation was enhanced, lag phase was significantly shorter in comparison with the control group. After a change in diet, significant elongation of the lag phase was observed. CONCLUSION: Diet change improves LDL resistance to oxidation and may influence prognosis in stroke patients.     

Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA

ObjectivesThe inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA).Materials and MethodsPRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants.ResultsIn healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited.ConclusionsWe showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.     

Pitfall of Light Transmission Aggregometry-Based Assessment of Platelet Function in Acute Ischemic Stroke Patients

Background: The utility of light transmission aggregometry (LTA)–based assessment of platelet function in acute ischemic stroke patients remains controversial. This study aimed to clarify why LTA failed to estimate platelet function in acute ischemic stroke patients. Methods: Using LTA, we evaluated the platelet aggregation abilities of citrated blood samples from 22 acute noncardiogenic ischemic stroke patients prior to treatment and compared them with those of 65 heathy volunteer controls. Platelet counts and mean platelet volumes (MPV) of citrated blood and platelet-rich plasma (PRP) prepared for LTA were evaluated simultaneously. Using a hematology analyzer, we also measured and compared the aggregation-prone properties of platelets in the hematology analysis process between patient and control samples. Results: Although platelets aggregated more easily and frequently in patient samples (P < .01), the maximum aggregation rate (MA%) of LTA was paradoxically lower in patients than in controls (P < .05). The PRP/citrated blood ratio of platelet counts and MPV were significantly lower in patients than in controls (P < .05). Conclusions: Our results suggest that MA% of LTA is erroneously displayed as lower values than the actual status in patients with increased platelet aggregation ability such as acute ischemic stroke because activated large platelets are preaggregated and thus decreased in the PRP on LTA.     

Platelet aggregation in focal cerebral ischemia – a clinical study

In a consecutive series of 35 patients with transient ischemic attacks (TIAs) 26 patients (74%) had pathological platelet aggregation 4 weeks after the latest TIA. Pathological platelet aggregation was the most frequent factor leading to a prophylactic treatment of the TIAs. Among 12 patients with reversible ischemic neurological deficit (RIND) only one had pathological platelet aggregation, and among 54 patients with completed stroke 37% had pathological platelet aggregation 4 weeks after the cerebral infarction.
It is possible by the antiaggregating agents acetylsalicylic acid and dipyridamole to normalize in vitro pathological platelet aggregation. The frequency of side effects was low. During this treatment further TIAs were stopped in 17/19 patients, and remission were seen in 14/14 stroke patients. Compared with the remissions during treatment with anticoagulants there was a tendency of more favouarble outcome in the group of stroke patients when treated with antiaggregating agents.     

Increased plasma glutamate in stroke patients might be linked to altered platelet release and uptake.

Experimental studies have shown the role of excitotoxicity in the pathogenesis of ischemic brain lesions, and glutamate levels have been found to be elevated in CSF and plasma from patients, early after stroke. In this study, we investigated whether platelets could be involved in the mechanism of altered plasma glutamate levels after stroke. Forty four patients, from 6 hours to 9 months after ischemic stroke, 15 age-related healthy controls and 15 controls with stroke risk factors or previous transient ischemic attack were enrolled. Glutamate plasma levels, platelet glutamate release after aggregation and platelet glutamate uptake were assessed. Plasma glutamate levels were increased up to 15 days after the ischemic event in stroke patients, and the levels at day 3 were inversely correlated with the neurologic improvement between day 3 and 15. Ex vivo platelet glutamate release was decreased by 70% in stroke patients, suggesting previous in vivo platelet activation. Moreover, platelet glutamate uptake in these patients was decreased by 75% up to 15 days and was still reduced 90 days after stroke. Our data show a prolonged increase of glutamate in plasma after stroke, which might presumably be linked to altered platelet functions, such as excessive release of the amino acid or impaired uptake.     

Platelet function tests in thrombotic cerebrovascular disorders

A variety of platelet function tests were performed in patients with four forms of obstructive cerebrovascular disease (CVD); transient ischemic attacks (TIA), reversible ischemic neurological deficit (RIND), cerebral infarct, and cerebral embolism of cardiac source in rheumatic valvular heart disease (RVHD). Platelet studies included platelet aggregation induced by ADP and ristocetin, spontaneous platelet aggregation, von Willebrand factor (VIII:vWF), platelet aggregation enhancing factor (PAEF), and percentage of large platelets (megathrombocytes). Serial testing was carried out in acute stroke patients. The effect of aspirin therapy was also evaluated. A clear difference in results was observed between patients with cardiogenic embolism and those with other forms of CVD. In patients with TIA, RIND, and cerebral infarct, platelet aggregation, both induced and spontaneous, was enhanced along with elevation of plasma VIII:vWF and PAEF, and increased percentage of megathrombocytes. In patients with cardiogenic embolism, however, these studies were negative except for percent megathrombocytes. This value was increased in the embolic patients with RVHD in comparison with non-embolic patients with RVHD. Increase in platelet aggregation to ADP and percent megathrombocytes developed slowly over a week following stroke. Induced and spontaneous platelet aggregation, and percent megathrombocytes could be normalized with 600 mg aspirin p.o. These studies suggest that a systemic increase of hyperaggregable platelets and of plasma activators of platelet function exists in thrombotic CVD and may be related to its pathogenesis, while local hemodynamic factors may be more important in the thrombogenesis of cardiogenic embolism.