氧化低密度脂蛋白及维生素E对人脐静脉内皮细胞分泌细胞因子的影响

目的:探讨OX-LDL和VitE对人脐静脉内皮细胞(HUVEC)分泌细胞因子IL-6、IL-8和TNF-α的影响。方法:以体外培养的HUVEC为模型,将OX-LDL与HUVEC孵育及HUVEC经VitE处理后再与OX-LDL孵育,应用ELISA试剂盒分别检测IL-6、IL-8和TNF-α水平。结果:内皮细胞加入OX-LDL干预后,IL-6、IL-8在6-12h开始高于对照组,24-36h达峰值,72h时仍较对照组高。TNF-α的释放在2-6h开始高于对照组,12h达峰值,36h明显下降,但仍较对照组高。并且OX-LDL在50、100、200μg/L时能呈剂量依赖性刺激内皮细胞产生IL-6、IL-8和TNF-α。VitE在50、100、200mg/L时能呈浓度依赖方式抑制OX-LDL引起的IL-6、IL-8、TNF-α产生,48h后OX-LDL+VitE组与OX-LDL组,内皮细胞分泌IL-6、IL-8和TNF-α水平无明显差异。结论:OX-LDL可促进血管内皮细胞产生炎性细胞因子IL-6、IL-8和TNF-α,而VitE在短时间内对上述效应有明显抑制作用。     

氧化低密度脂蛋白自身抗体与冠心病的关系

目的:探讨氧化低密度脂蛋白自身抗体(ox-LDL Ab)与冠心病及低密度脂蛋白(LDL)的关系。方法:提取血清,用ELISA方法测定ox-LDL Ab滴度。结果:冠心病患者ox-LDL Ab滴度明显高于正常对照组(P<0 05);ox-LDL Ab与LDL直线相关(r=0.3338,P<0.05)。结论:ox-LDL Ab与冠心病有明显相关性,自身免疫反应可能参与动脉粥样硬化的形成。     

维生素E对氧化低密度脂蛋白诱导的单核细胞/内皮细胞粘附的干预作用

目的:观察ox-LDL在体外对兔单核细胞与血管内皮细胞粘附的影响及维生素E的干预作用,初步探讨其机制。方法:培养兔主动脉内皮细胞。密度梯度离心法分离健康兔单核细胞。沉淀法制备人LDL,硫酸铜氧化制备ox-LDL。用Kim等^[1]方法并略加改良观察ox-LDL对内皮细胞/单核细胞粘附的影响及维生素E的干预。Northernblot检测内皮细胞VCAM-1mRNA的表达。结果:ox-LDL浓度为2.5mg/L、5mg/L、10mg/L时,每个视野粘附的单核细胞数分别为132.8±20.2、350.0±37.2、502.6±78.8,而正常对照组为51.2±7.7,相差非常显著(P＜0.01)。在加ox-LDL(10mg/L)前加维生素E干预,当维生素E浓度为10μmol/L、20μmol/L、40μmol/L时,粘附单核细胞数分别为422.3±32.2、298.0±21.7、205.2±36.6,均低于ox-LDL对照组的502.6±78.8,维生素E浓度为10μmol/L组与对照组相差不显著(P＞0.05),其余两组与ox-LDL对照组相差非常显著(P＜0.01)。ox-LDL对照组内皮细胞VCAM-1mRNA表达高于维生素E(40μmol/L)干预组(0.49±0.09vs0.33±0.10,P＜0.05)。结论:ox-LDL促进兔主动脉内皮细胞与单核细胞的粘附,其机制与其促进内皮细胞表达VCAM-1有关。维生素E能抑制ox-LDL的上述作用。     

载脂蛋白E基因多态性与血脂代谢及冠心病的关系

目的：研究载脂蛋白E基因多态性对血脂代谢的影响及其与冠心病的关系。方法：运用PCR－PFLP方法检测168例江苏地区无血缘健康汉族人群。分析健康人群各基因型及等位基因对血脂、载脂蛋白及脂蛋白（a）的影响,同时测定63全冠心病患者载脂蛋白E基因型,并与性别相匹配的90例正常对照组比较各基因型及等位基因频率分布。结果：载脂蛋白E各基因型血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL－C）及载脂蛋白B（ApoB）水平由高到低依次为ε3／4＞ε3／3＞ε2／3;各等位基因TC、LDL－C及ApoB水平由高到低依次为ε4＞ε3＞ε2。ε2等位基因具有明显的降低TC、LDL－C和ApoB的作用,而ε4等位基因明显的升高TC、LDL－C和ApoB的作用。冠心病组ε4等位基因频率（12.70%）明显高于对照组（5.55%）。结论：载脂蛋白E基因多态性影响血脂及载旨蛋白水平。ε2 基因具有明显的降低TC、LDL－C和ApoB的作用,而ε4等位基因的作用正相反。ε4等位基因可能是冠心病的遗传易患因子。     

氧化修饰的低密度脂蛋白与动脉粥样硬化

ＡＳ的发生机制一直是一个热门课题，而氧化修饰的低密度脂蛋白在ＡＳ硬化的形成过程中扮演着一个非常重要的角色。本文从免疫学、病理学等最新的角度对ＡＳ的形成及氧化修饰的低密度脂蛋白在其中的作用作一简述。     

前列腺素E2对LDL氧化修饰和巨噬细胞清道夫受体活性的影响

应用ＢＡ－ＥＬＩＳＡ酶联免疫技术、免疫组化和油红Ｏ组织化学等方法观察了氧化ＬＤＬ对巨噬细胞清道夫受体活性的影响和前列腺素Ｅ＿２（ＰＧＥ＿２）等的保护作用。结果显示，氧化ＬＤＬ组的巨噬细胞含脂量、清道夫受体活性及免疫组化阳性颗粒三项指标均明显高于ＰＧＥ＿２和亚硒酸钠两用药组。表明ＰＧＥ＿２和亚硒酸钠均有明显抗氧化作用，而ＰＧＥ＿２作用还略优于抗氧化剂亚硒酸钠。     

脂蛋白对肾小球膜细胞产生血小板活化因子的影响

我们利用体外培养的正常人肾小球系膜细胞，观察了纯化的人低密度脂蛋白和高密度脂蛋白对该细胞产生上板活化因子的影响。结果发现：经刺激２０ｈ在一定浓度范围内，低密度脂蛋白能增加增减系膜细胞上清液中血小板活化因子的含量，且在浓度为１００μｇ／ｍｌ时，培养细胞上清液中血小板活化因子的上升显著，在２００μｇ／ｍｌ，达到高峰，而高密度脂蛋白则在高浓度（３５０μｇ／ｍｌ）时有轻度刺激作用，这些结果说明：Ｗ氏密度脂     

冠心病患者血浆氧化修饰低密度脂蛋白与血清铁蛋白关系的研究

对５３例冠心病患者及３０例正常人血浆氧化修饰低密度脂蛋白（ＯＸ－ＬＤＬ）与血清铁蛋白（ＳＦ）进行了测定，结果显示：冠心病患者血浆ＯＸ－ＬＤＬ和ＳＦ水平平均显著高于正常对照组（Ｐ〈０．００１和Ｐ〈０．０５），且两者呈显著正相关（ｒ＝０．４８５，Ｐ〈０．００１），冠心病患者血浆ＯＸ－ＬＤＬ水平升高可能与体内铁贮存增加有关。     

硒、维生素E联用对高胆固醇血症家兔血液流变性的影响

对高胆固醇血症家兔应用硒（Ｓｅ）、维生素Ｅ（ＶＥ）前后血液流变性、过氧化脂质（ＬＰＯ）、谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）和超氧化物歧化酶（ＳＯＤ）、血栓素（ＴＸＡ２）、前列环素（ＰＧＩ２）进行观察。发现Ｓｅ或ＶＥ及Ｓｅ、ＶＥ联用可不同程度降低高胆固醇家兔红细胞压积和红细胞聚集性，增加红细胞变形性，降低血清ＬＰＯ含量、ＴＸＡ２／ＰＧＩ２比值和ＴＸＡ２水平，提高ＧＳＨ－Ｐｘ、ＳＯＤ活力和ＰＧＩ２水平。提示Ｓｅ和ＶＥ有降低血液粘稠度作用，Ｓｅ、ＶＥ联用组效果优于Ｓｅ或ＶＥ单用组。     

氧化修饰的低密度脂蛋白和极低密度脂蛋白对单核细胞MCP-1表达的影响

为了研究氧化修饰的低密度脂蛋白（ＯＸ┐ＬＤＬ）和氧化修饰的极低密度脂蛋白（ＯＸ┐ＶＬＤＬ）对单核细胞的单核细胞趋化蛋白１（ＭＣＰ┐１）ｍＲＮＡ和蛋白表达的影响。在单核细胞的培养基中分别加入２５μｇ／ｍｌ的ＬＤＬ、ＯＸ┐ＬＤＬ、ＶＬＤＬ和ＯＸ┐ＶＬＤＬ，培养２４小时后分别收集单核细胞及其条件培养基。参照异硫氰酸胍法提取单核细胞总ＲＮＡ，并用γ３２Ｐ末端标记ＭＣＰ┐１寡核苷酸探针，进行ｓｌｏｔｂｌｏｔ和Ｎｏｒｔｈｅｒｎｂｌｏｔ分析。同时用夹心ＥＬＩＳＡ检测其条件培养基中ＭＣＰ┐１蛋白含量。结果显示单核细胞能表达ＭＣＰ┐１，ＯＸ┐ＬＤＬ和ＯＸ┐ＶＬＤＬ能明显增强单核细胞表达ＭＣＰ┐１。而ＬＤＬ和ＶＬＤＬ的作用却很轻微。说明单核细胞能通过表达ＭＣＰ┐１，从而进一步招引其它的单核细胞迁入内皮下间隙，而ＯＸ┐ＬＤＬ和ＯＸ┐ＶＬＤＬ能加强这种作用。     

糖尿病患者冠状动脉血管成形术后血小板活性的变化

目的:观察糖尿病患者经皮冠状动脉介入术(PCI)后的血小板活化水平的变化。方法:应用酶联免疫法和放射免疫法测定15例糖尿病患者和57例非糖尿病患者的术前术后血浆11-DH-TXB₂和血小板内cAMP的浓度来反映血小板活化水平,并比较其变化。结果:两组患者手术前后的11-DH-TXB₂升高和cAMP降低水平,术后糖尿病患者的11-去氢-血栓素B₂(11-DH-TXB₂)高于非糖尿病患者,而糖尿病患者的cAMP低于非糖尿病患者。结论:糖尿病患者PCI后血小板活化水平明显高于非糖尿病患者。     

The oxidation ratio of LDL: a predictor for coronary artery disease

Objective: Oxidized LDL cholesterol (ox-LDL-C) is considered to be a key factor of initiating and accelerating atherosclerosis (AS). The purpose of this study is to elucidate the sensitivity and specificity of ox-LDL and oxidation ratio of LDL in the diagnosis of coronary artery disease (CAD). For the first time, we investigated the ratio of ox-LDL to ALB(ox-LDL/ALB). Methods and results: Blood ox-LDL, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and albumin (ALB) were measured in patients with acute myocardial infarction (AMI, n = 80), unstable angina pectoris (UAP, n = 80), stable angina pectoris (SAP, n = 80), normal control (n = 60), and dyslipidemia control (n = 60). Ox-LDL was measured by competitive ELISA. The level of ox-LDL and oxidation ratio of LDL(ox-LDL/TC, ox-LDL/HDL-C, ox-LDL/ LDL-C and ox-LDL/ALB) were significantly higher in each diseased group than controls (P < 0.001). In CAD group, ox-LDL and oxidation ratio of LDL in subjects complicated with hypertension (HT) and/or diabetes mellitus (DM) increased further (P < 0.001). Ox-LDL/ALB in the AMI group was 7 times higher than normal control group (0.068 ± 0.017 vs 0.009 ± 0.007, P < 0.001). The area under the curve (AUC) of receiver operating characteristic curve (ROC curve) is a criterium to evaluate the accuracy of diagnosing a disease. The AUC of ROC curve of ox-LDL/TC, ox-LDL/HDL-C, ox-LDL, ox-LDL/ALB and ox-LDL/ LDL-C for diagnosing CAD were 0.975, 0.975, 0.966, 0.966, 0.957 respectively (P < 0.001). When ox-LDL/TC = 0.175, the sensitivity and specificity of diagnosing CAD were 0.917 and 0.925, which were almost equal to each other, indicating that the rates of missed diagnosis and misdiagnosis for CAD were the lowest. Conclusions: The level of ox-LDL and the ratio of ox-LDL/TC, ox-LDL/LDL-C, ox-LDL/HDL-C and ox-LDL/ALB are better biomarkers than TC, TG, HDL-C and LDL-C for discriminating between patients with coronary artery disease and healthy subjects. And patients who have a high ratio of ox-LDL /TC may have a higher risk for CAD.     

冠心病患者血小板聚集和心功能关系的研究

本文观察了肾上腺素诱导的全血血小板聚集活性和心功能指标的关系。结果表明：血小板聚集性和每搏输出量呈非常显著负相关（Ｐ＜０．００１），和射血前期／左室射血时间（ＰＥＰ／ＬＶＥＴ，等容收缩期／左室射血时间呈显著正相关（Ｐ＜０．００２），与心舒早期功能指标无显著相关。因此，监测血小板聚集性的动态变化对了解心脏收缩功能和预报心肌梗塞，心性猝死发生的危险性具有一定的临床价值。     

The effect of LDL apheresis on progression of coronary artery disease in patients with familial hypercholesterolemia

This study investigated the effect of extracorporal lipid-lowering therapy by low-density lipoprotein (LDL) apheresis on coronary artery disease in a population characterized by early development and rapid progression of atherosclerosis. We treated 32 patients aged between 15 and 63 years with drug-refractory familial hypercholesterolemia, treated once a week by immuno-specific LDL apheresis for 3 years in a controlled prospective and non-randomized trial; 25 patients (14 females and 11 males) completed the study. Noninvasive data were obtained by physical examination, 12-lead ECG and exercise testing. Invasive cardiological data were obtained by cardiac catheterization according to a standardized protocol in four cardiological centers. Left ventricular ejection fraction was calculated using planimetry. Coronary stenoses were measured quantitatively in 23 defined coronary segments by a panel of four investigators with an electronic digital caliper. In addition, overall coronary atherosclerosis was visually qualified. Final decisions on a classification into one of three groups (regression, no change, progression) of coronary atherosclerosis were based on panel consensus. Six cardiac events occurred throughout the study: percutaneous transluminal coronary angioplasty in one patient, coronary bypass grafting in three and two deaths. Statistical analysis of exercise testing yielded no significant change for maximum power and work capacity during the study period. Hemodynamic data revealed no significant change; mean ejection fraction was calculated as 65.8 ± 15.9% at study entry and 67.0 ± 12.7% at completion. Quantitative measurement of 111 circumscribed coronary stenoses showed a mean stenosis degree of 45 ± 26% at entry cineangio-film and 43 ± 22% at final cineangio-film demonstrating no significant change. Eight localized stenoses showed a regression of more than 10% and 11 stenoses a progression of more than 10%. Panel consensus decision for overall coronary atherosclerosis resulted in regression in no patients, no change in 16, questionable progression in 3, definite progression in 5, and undecided in one. We conclude that specific LDL-apheresis therapy can be used effectively for primary and secondary prevention of coronary artery disease in patients with familial hypercholesterolemia. Its beneficial effect was the prevention of further progression of coronary artery disease in the majority of the study population.Abbreviations FH familial hypercholesterolemia - LDL low-density lipoprotein     

Impact of a 1-year lifestyle modification program on plasma lipoprotein and PCSK9 concentrations in patients with coronary artery disease

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Effect of nondipper hypertension on coronary artery disease progression in patients with chronic coronary syndrome

Background/aimIt has been suggested that there is a significant progress in coronary artery disease (CAD) by many pathophysiological mechanisms. Nondipper hypertension (NDH) has been shown to have higher target organ damage and have a higher rate of cardiovascular mortality and morbidity. In this study, we investigated the effect of nondipper hypertension on the progression of coronary atherosclerosis.Materials and methodsA total of 186 patients who underwent coronary angiography twice between 6 months and 3 years were included in the study. Coronary angiography was repeated on the admission day due to angina or positive exercise test and the patients were divided into groups.ResultsProgression of coronary artery disease was detected in 58 of 186 patients. Seventy-one of the total patients were found to be nondipper hypertensive. Nondipper hypertension, hypertension, diabetes mellitus, low-density lipoprotein, and total cholesterol were found to be effective in the progression of CAD. Among these parameters, it was seen that nondipper hypertension and hyperlipidemia were the most important independent risk factors.Conclusion Coronary artery disease is a progressive disease, and this progression depends on many reasons. In our study, we showed that nondipper hypertension is a new parameter that is effective in CAD progression.     

The influence of aerobic fitness status on ventilatory efficiency in patients with coronary artery disease

OBJECTIVE:

To test the hypotheses that 1) coronary artery disease patients with lower aerobic fitness exhibit a lower ventilatory efficiency and 2) coronary artery disease patients with lower initial aerobic fitness exhibit greater improvements in ventilatory efficiency with aerobic exercise training.

METHOD:

A total of 123 patients (61.0±0.7 years) with coronary artery disease were divided according to aerobic fitness status into 3 groups: group 1 (n = 34, peak VO₂<17.5 ml/kg/min), group 2 (n = 67, peak VO₂>17.5 and <24.5 ml/kg/min) and group 3 (n = 22, peak VO₂>24.5 ml/kg/min). All patients performed a cardiorespiratory exercise test on a treadmill. Ventilatory efficiency was determined by the lowest VE/VCO₂ ratio observed. The exercise training program comprised moderate-intensity aerobic exercise performed 3 times per week for 3 months. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02106533","term_id":"NCT02106533"}}NCT02106533

RESULTS:

Before intervention, group 1 exhibited both lower peak VO₂ and lower ventilatory efficiency compared with the other 2 groups (p<0.05). After the exercise training program, group 1 exhibited greater improvements in aerobic fitness and ventilatory efficiency compared with the 2 other groups (group 1: ▵ = -2.5±0.5 units; group 2: ▵ = -0.8±0.3 units; and group 3: ▵ = -1.4±0.6 units, respectively; p<0.05).

CONCLUSIONS:

Coronary artery disease patients with lower aerobic fitness status exhibited lower ventilatory efficiency during a graded exercise test. In addition, after 3 months of aerobic exercise training, only the patients with initially lower levels of aerobic fitness exhibited greater improvements in ventilatory efficiency.     

老年冠状动脉粥样硬化性心脏病患者冠状动脉病变影响因素的探讨

目的探讨循环人血管紧张素1～7(Ang1～7)、内皮细胞微颗粒CD31^＋、单核细胞CD14^＋CD16^＋和超敏C－反应蛋白(hs－CRP)对老年冠状动脉粥样硬化性心脏病患者冠状动脉病变的影响。 方法选择2010年1月至2014年3月老年冠状动脉粥样硬化性心脏病患者140例,健康对照组50例。根据冠状动脉狭窄程度将患者分为3组：75%～84%组,85%～94%组和95%～100%组;根据冠状动脉病变支数将患者分为4组：单支、双支、三支和四支病变组;再根据美国纽约心脏病学会(NYHA)分级将患者分为4组：NYHAⅠ、Ⅱ、Ⅲ、Ⅳ级组;又根据左心室射血分数(LVEF)进一步将患者分为3组：48%～58%组、36%～47%组和25%～35%组;根据6 min步行试验的步行距离又将患者分为3组：>450 m组、150～450 m组和<150 m组。采用流式细胞术检测血清CD31^＋和CD14^＋CD16^＋水平的变化,使用双夹心抗体酶联免疫吸附法定量检测Ang1～7水平,应用免疫散射比浊法测定hs－CRP的水平。多组间差异采用单因素方差分析,组间两两比较采用t检验。 结果冠状动脉狭窄75%～84%组Ang1～7(34.8±6.9)pg/mL、CD31^＋(471±29)个/μL、CD14^＋CD16^＋(1.4±0.3)%、hs－CRP(1.7±0.8)mg/L分别与冠状动脉狭窄95%～100%组Ang1～7(9.1±0.4) pg/mL、CD31^＋ (1554±40)个/μL、CD14^＋CD16^＋(5.9±0.8)%、hs－CRP(17.1±1.5) mg/L比较,差异均有统计学意义(P值均小于0.05);冠状动脉单支病变组Ang1～7(38.7±7.9)pg/mL、CD31^＋(496±30)个/μL、CD14^＋CD16^＋(2.1±0.7)%、hs－CRP(1.9±0.9)mg/L与分别冠状动脉四支病变组Ang1～7(11.2±2.0)pg/mL、CD31^＋(1583±52)个/μL、CD14^＋CD16^＋(10.6±1.4)%、hs－CRP(14.9±1.9)mg/L比较,差异均有统计学意义(P值均小于0.05);NYHAⅠ级组Ang1～7(38.5±2.7)pg/mL、CD31^＋(511±32)个/μL、CD14^＋CD16^＋(1.7±0.5)%、hs－CRP(1.9±0.2)mg/L与分别NYHA Ⅳ级组Ang1～7(10.0±1.2)pg/mL、CD31^＋(1598±49)个/μL、CD14^＋CD16^＋(12.1±1.4)%、hs－CRP(15.0±1.9)mg/L比较,差异均有统计学意义(P值均小于0.05);LVEF 48%～58%组Ang1～7(32.9±6.8)pg/mL、CD31^＋(385±28)个/μL、CD14^＋CD16^＋(2.9±0.8)%、hs－CRP(2.1±0.8)mg/L与分别LVEF 25%～35%组Ang1～7(9.5±2.0)pg/mL、CD31^＋(1644±54)个/μL、CD14^＋CD16^＋(13.0±1.6)%、hs－CRP(14.1±2.0)mg/L比较,差异均有统计学意义(P值均小于0.05);6 min步行试验>450 m组Ang1～7(36.4±7.1)pg/mL、CD31^＋(561±30)个/μL、CD14^＋CD16^＋(1.9±0.5)%、hs－CRP(2.1±0.9)mg/L与分别6 min步行试验<150 m组Ang1～7(10.1±0.9)pg/mL、CD31^＋(1338±41)个/μL、CD14^＋CD16^＋(7.2±0.9)%、hs－CRP(18.7±1.5)mg/L比较,差异均有统计学意义(P值均小于0.05)。 结论Ang1～7水平下降,CD31^＋、CD14^＋CD16^＋和hs－CRP表达水平的增高可能影响老年冠状动脉病变的严重程度。