血管内皮祖细胞生物学活性与血管内皮祖细胞捕获支架的研究进展

血管内皮祖细胞（EPCs）作为内皮细胞的前体细胞,具有"持续"的自我更新及定向分化的能力。EPCs捕获支架,如表面包被CD34^＋抗体的支架,能够识别循环血液中EPCs表面特异性性结合位点,捕获并促使EPCs归巢、分化为内皮细胞,参与病变血管内皮修复、促进血管新生、改善冠脉血流。EPCs的生物学活性是决定EPCs捕获支架临床应用的关键,本文从EPCs生物学特性、功能、冠状动脉微环境对EPCs的调控机制、EPCs捕获支架的研究进展等方面进行综述,探讨EPCs捕获支架的治疗价值。     

冠状动脉慢血流患者外周血内皮祖细胞数量的变化

目的:观察冠状动脉慢血流患者外周血内皮祖细胞(EPCs)数量的变化.方法:选择26例冠状动脉造影证实为慢血流的患者为CSF组,冠脉造影血流正常的患者20例为NCF组.以校正TIMI帧数＞27诊断为冠状动脉慢血流.分别抽取外周血进行EPCs的分离培养,于第10天对EPCs进行鉴定,并于倒置像差显微镜下计数EPCs克隆形成单位,评估两组患者外周血EPCs水平的差异.结果:(1)两组在年龄、性别、吸烟史、高血压、糖尿病、冠心病家族史、血脂方面均无明显统计学差异(P＞0.05);(2)CSF组外周血EPCs水平较NCF组明显下降(11.2±2.9 vs.17.1±2.4),差异有统计学意义(P＜0.01).结论:冠状动脉慢血流患者外周血EPCs数量减少.     

Targeting HIV latency: resting memory T cells,hematopoietic progenitor cells and future directions

Current therapy for HIV effectively suppresses viral replication and prolongs life, but the infection persists due, at least in part, to latent infection of long-lived cells. One favored strategy toward a cure targets latent virus in resting memory CD4⁺ T cells by stimulating viral production. However, the existence of an additional reservoir in bone marrow hematopoietic progenitor cells has been detected in some treated HIV-infected people. This review describes approaches investigators have used to reactivate latent proviral genomes in resting CD4⁺ T cells and hematopoietic progenitor cells. In addition, the authors review approaches for clearance of these reservoirs along with other important topics related to HIV eradication.     

黄芪对动脉粥样硬化兔骨髓内皮祖细胞生长的影响

目的:研究黄芪对冠状动脉粥样硬化模型兔骨髓内皮祖细胞(endothelial progenitor cells,EPCs)生长的影响,并探讨黄芪对冠心病临床治疗的可能机制。方法:建立动脉粥样硬化模型,分为正常对照组和动脉粥样硬化组,体外分离培养EPCs,通过荧光显微镜观察细胞经乙酰化低密度脂蛋白(DiI-ac-LDL)摄取试验和荆豆凝集素(FITC-UEA-I)和体外成血管试剂matrigel观察细胞成血管功能来鉴定EPCs,检测细胞黏附能力、迁移能力及增殖能力。结果:动脉粥样硬化组兔冠状动脉可见斑块或脂纹;DiI-ac-LDL和FITC-UEA-I双染色阳性;培养6d的EPCs可见血管腔样的结构;动脉粥样硬化组EPCs的数量、黏附、迁移及增殖能力较正常对照组明显下降,差异有显著性(P<0.05)。黄芪可以一定程度上促进动脉粥样硬化组兔骨髓EPCs的数量的增加及黏附、迁移和增殖能力,并以20g/L最为明显,差异有显著性(P<0.05)。结论:黄芪治疗冠心病的作用机制可能为促进EPCs的生长。     

对磁粒子标记内皮祖细胞移植至兔颈动脉粥样硬化模型局部行磁共振活体成像的可行性

目的 探讨纳米磁粒子偶联物Fe2O3-PLL标记的内皮祖细胞(EPCs)移植至兔颈动脉粥样硬化模型局部行磁共振活体成像的可行性.方法 制备Fe2O3-PLL,标记分离纯化后得到的兔外周血EPCs,普鲁士蓝染色显示细胞内铁;高脂饮食联合球囊扩张制作兔动脉粥样硬化模型18只,随机分成3组,制模7周后,经股动脉插管分别将标记细胞、未标记细胞及等量生理盐水移植至模型兔右侧颈动脉局部,在移植前、移植后1、7、14天行MR活体成像,测量血管腔内信噪比(SNR),并与细胞移植后各时间点血管组织切片的普鲁士蓝染色比较.结果 普鲁士蓝染色显示蓝色铁颗粒位于EPCs胞浆内,Fe2O3-PLL对EPCs的标记率接近100%;与移植前相比,标记细胞移植组、未标记细胞移植组和对照组移植后各时间点的SNR差异均无统计学意义.血管组织的普鲁士蓝染色结果显示,仅移植后1天的血管局部可见少量蓝染颗粒.结论 在动脉粥样硬化形成过程中移植EPCs,不能使其在局部停留.     

冠心病患者血管内皮功能与冠状动脉病变严重程度的关系

目的 探讨冠心病患者的血管内皮功能改变及其与冠状动脉病变严重程度的关系.方法 73例拟行冠状动脉造影术的患者,根据冠状动脉造影结果将其分为冠心病组39例和非冠心病组34例.13例健康、无冠心病危险因素者作为对照组.运用高频线阵超声测定肱动脉流量介导的血管扩张作用指标流量介导血管扩张比(FMD)及硝酸酯介导的血管扩张作用指标硝酸酯介导血管扩张比(NTG-MD),评估患者的血管内皮功能状况,以探讨血管内皮功能与冠状动脉狭窄间的关系.结果 冠心病组、非冠心病组和对照组的FMD分别为(4.81±2.33)%、(9.29±3.88)%和(13.58±1.80)%,3组间两两比较差异均有统计学意义(F值为48.012,P＜0.01);NTG-MD分别为(13.72±3.27)%、(15.64±2.65)%、(16.54±2.98)%,3组问差异有统计学意义(F值为6.015,P＜0.01),冠心病组与其余2组相比差异均有统计学意义(P均＜0.05).FMD与管径基础值、冠状动脉受累支数及冠状动脉最大狭窄程度呈负相关(r分别为-0.224、-0.316、-0.721,P分别为0.038、0.003和＜0.001).NTG-MD与管径基础值、冠状动脉受累支数及冠状动脉最大狭窄程度亦呈负相关(r分别为-0.483、-0.258、-0.372,P分别为＜0.001、0.027、0.001).多项逐步回归分析显示FMD与冠状动脉最大狭窄程度、管径基础值呈线性关系(r分别为-0.012、-0.022,P均＜0.001).NTG-MD与管径基础值及冠状动脉最大狭窄程度呈线性关系(r分别为-0.032、-0.0073.P均＜0.001).结论 冠心病患者内皮损害程度与冠状动脉狭窄严重程度之间呈线性相关.     

CD31+/Annexin V+ microparticles in healthy offsprings of patients with coronary artery disease

Background  First-degree relatives of patients with premature coronary artery disease (CAD) develop endothelial dysfunction even in the case they are apparently healthy. In this study we wanted to clarify whether reduced blood levels of circulating endothelial progenitor cells (EPCs), an endogenous repair mechanism to replace dysfunctional endothelium, or elevated endothelial-derived microparticles (EMPs), an indicator and a mediator of increased endothelial cell damage/apoptosis, are an initial step in the pathogenesis of endothelial dysfunction in genetically predisposed subjects.
Materials and methods  Fifty-six healthy young men (aged 23 to 31 years) from a fire brigade were enrolled, of which 20 subjects had a positive family history (FH) for premature CAD. Subjects with or without a positive FH did not differ with respect to age, body mass index, risk factors and C-reactive protein. Endothelial function was assessed by hyperaemia-mediated relaxation of the brachial artery, blood levels of EPCs (VEGFR2⁺CD34⁺ cells) and number of EMPs (CD31^+(bright)/Annexin V⁺ particles) were analysed by flow cytometry.
Results  Hyperaemia-mediated relaxation of the brachial artery was similar in both groups, and the blood levels of EPCs were comparable. However, the number of EMPs were significantly increased in subjects with a positive FH compared to those with a negative FH (neg. FH: 55·31 ± 4·88 vs. pos. FH: 70·37 ± 6·32 particles µL⁻¹ platelet poor plasma; P  < 0·05). Number of EMPs correlate inversely with the FMD response.
Conclusions  These results suggest that increased plasma levels of EMPs may be an initial step in the development of endothelial dysfunction in genetically predisposed subjects.     

基质细胞衍生因子预处理的内皮祖细胞对大鼠急性心肌梗死的治疗作用

目的 探讨基质细胞衍生因子(stromal cell-derived factor-1,SDF-1)预处理的内皮祖细胞(endothelial progenitor cells,EPCs)对大鼠急性心肌梗死的治疗作用.方法 培养大鼠骨髓来源的内皮祖细胞,检测SDF-1在体外对EPCs迁移和存活能力的影响.建立大鼠急性心肌梗死模型,随机分为SDF-1+EPCs组、EPCs组和对照组,每组12只.心梗后24 h,将SDF-1预处理或未处理的EPCs经尾静脉注入动物体内,对照组注射不含细胞的培养基.细胞输注后的14 d和28 d,分别检测血管密度、心功能及心肌梗死面积等指标.结果 细胞输注后14 d,SDF-1+EPCs组血管密度高于EPCs组及对照组.细胞输注后28 d,SDF-1+EPCs组大部分心功能指标优于EPCs组和对照组,心梗而积低于EPCs组和对照组.结论 SDF-1预处理能促进EPCs的迁移和存活,促进体内EPCs介导的新血管生成,减少心肌梗死面积,促进心功能的恢复.     

冠心病患者冠状动脉病变严重程度与内皮祖细胞及血管内皮功能的相关性分析

目的探讨冠心病患者循环血内皮祖细胞(EPCs)数量、血流介导的内皮依赖性血管舒张功能(FMD)的变化及其与冠状动脉病变严重程度的相关性。方法对159例患者根据冠状动脉造影结果,分为冠心病组(101例)及对照组(58例),采用流式细胞术检测所有入选者EPCs水平,并采用高分辨率血管超声法检测其肱动脉FMD。冠心病组依据SYNTAX积分进一步分为低危、中危和高危3个亚组,比较高危、中危、低危三组之间EPCs数量及FMD的差异及与冠状动脉病变程度的相关性。结果与对照组比较,冠心病组患者EPCs数量显著减少,肱动脉FMD亦明显减低(P<0.05),循环血EPCs数量与肱动脉FMD呈显著正相关趋势(r=0.41,P<0.01)。各亚组之间,低危组与高危组比较,EPCs数量水平及FMD有统计学差异(P<0.05),中危组与低危组、中危组与高危组之间比较,EPCs数量水平及FMD均无显著性差异(P>0.05)。EPCs数量及FMD均与冠状动脉造影SYNTAX评分呈负相关(r=-0.381,P<0.01;r=-0.317,P<0.01)。结论冠心病患者循环血EPCs数量较健康人群显著减少,血管内皮功能显著低下,且与冠状动脉病变严重程度呈负相关。     

Endothelial progenitor cells: new perspectives and applications in cardiovascular therapies

For over 10 years, bone marrow-derived endothelial progenitor cells (EPCs) have been studied as a novel biomarker to assess the severity of cardiovascular diseases, and as a potential new strategy in regenerative medicine. Cell-based therapy to stimulate postnatal vasculogenesis or to repair vascular integrity is being evaluated for cardiovascular diseases with excess morbidity and mortality, including ischemic heart disease, in-stent restenosis, pulmonary hypertension and peripheral arterial occlusive disease. Although clinical experience is still limited, observed effects appear modest compared with preclinical models. In this review, we will examine major hurdles to the effective use of EPCs, including our incomplete understanding of the characterization and dysfunctional phenotype of circulating EPCs in pathological conditions. Understanding the basic mechanisms of EPC dysfunction will be a prerequisite in enhancing their therapeutic potential.     

雷帕霉素洗脱支架在血小板高度活化状态冠状动脉介入治疗的疗效评价

目的:评价雷帕霉素药物洗脱支架治疗冠心病并血小板高度活化状态冠状动脉狭窄的疗效。方法:回顾202例冠心病患者行冠状动脉内支架介入治疗,其中131例为冠心病并血小板高度活化状态,采用雷帕霉素药物洗脱支架治疗62例,采用普通支架治疗69例;71例为冠心病不伴血小板高度活化状态,均为雷帕霉素药物洗脱支架治疗。结果:随访12个月,冠心病并血小板高度活化状态雷帕霉素药物洗脱支架治疗组,心脏事件发生率8.06%,普通支架治疗组心脏事件发生率10.14%,2组比较差异有统计学意义(P<0.01)。血小板高度活化状态冠状动脉再狭窄率比较,雷帕霉素药物洗脱支架治疗组11.29%,普通支架治疗组15.94%,2组比较差异有统计学意义(P<0.01)。结论:雷帕霉素药物洗脱支架能有效防止血小板高度活化状态冠状动脉病变新生内膜增殖和再狭窄,提高冠状动脉支架术的成功率,降低心脏事件发生率。     

冠心病合并高血压患者眼底动脉粥样硬化的相关研究

目的观察冠心病合并高血压患者冠状动脉粥样硬化与眼底动脉粥样硬化发生是否相关。方法观察60例经冠状动脉造影确诊的冠心病合并高血压的患者眼底动脉硬化情况,并同时进行对照分析。结果冠心病合并高血压患者眼底动脉粥样硬化发生率高于其他患者。结论冠心病合并高血压患者动脉粥样硬化与眼底动脉粥样硬化有密切关系,眼底动脉检查是了解冠状动脉硬化的较方便的方法。     

冠心病患者凝血及纤溶系统机能改变的临床研究

对２０例健康人，２０例稳定性心绞痛（ＳＡ），１９例不确定型心绞痛（ＵＡ）与５７例急性心肌梗塞（ＡＭＩ）等患者，进行了组织型纤溶酶原激活物（ｔ－ＰＡ）组织型纤酶原激活抑制物（ＰＡＩ），纤溶酶原（ＰＬＧ），α２抗纤溶酶（α２ＡＰ）纤维蛋白原（ＦＧ）与Ｄ－二聚体（Ｄ－Ｄｉｍｅｒ）等指标的活性或含量的测定，结果：与健康人相比，ＵＡ和ＡＭＩ患者发病时，ｔ－ＰＡ活性及ｔ－ＰＡ／ＰＡＩ比值均明显降低（Ｐ值均〈０     

无创性超声测定冠状动脉支架术后再狭窄患者血管内皮功能和循环内皮祖细胞水平

目的运用无创性超声诊断技术测定经皮冠状动脉介入术（PCI）治疗急性心肌梗死（AMI）愈后冠状动脉支架再狭窄（ISR）患者的血管内皮功能,并探讨血管内皮功能与循环内皮祖细胞（EPCs）水平变化特点。 方法选取2009—2015年川北医学院附属医院收治的完成冠状动脉造影随访的急性心肌梗死（AMI）后行PCI治疗患者220例。29例患者PCI治疗AMI后发生ISR（ISR组）,191例患者PCI治疗AMI后未发生ISR（非ISR组）。采用高频超声技术获取患者肱动脉内皮依赖性功能（FMD）、非内皮依赖性功能（NMD）和颈动脉内膜中层厚度（IMT）,同时检测循环EPCs表达水平。用独立样本t检验比较ISR组与非ISR组患者IMT、FMD、NMD、CD133＋/KDR＋EPCs、CD34＋/KDR＋EPCs、CD34＋EPCs、CD133＋EPCs、KDR＋EPCs水平差异;采用单因素及多因素非条件Logistic回归分析筛选冠状动脉ISR的独立预测因子。 结果ISR组患者糖化血红蛋白（HbA1c）、尿素氮、肌酐浓度均高于非ISR组患者,且差异均有统计学意义（t值分别为-1.769、-3.671、2.77,P均<0.05）,血管紧张素转化酶抑制剂/血管紧张素受体拮抗剂、周围血管扩张剂、胰岛素、利尿剂使用率均高于非ISR组患者,硝酸甘油使用率低于非ISR组患者,且差异均有统计学意义（χ²值分别为3.832、6.567、2.072、16.540、4.949,P均<0.05）。2组患者IMT、FMD差异均无统计学意义,但ISR组患者NMD低于非ISR组患者,且差异有统计学意义（t=2.338,P均<0.05）。2组患者CD34＋EPCs、CD133＋EPCs水平差异均无统计学意义;ISR组患者CD34/KDR＋EPCs、CD133/KDR＋EPCs、KDR＋EPCs水平均较非ISR组患者降低,且差异均有统计学意义（t值分别为2.298、3.986、2.106,P均<0.05）。Logistic回归分析结果显示,HbA1c浓度、硝酸甘油使用率、利尿剂使用率、NMD是ISR的独立预测因子。 结论阶段性血糖水平等危险因素控制不良,损害血管壁功能,减少循环EPCs数量,结合老年冠状动脉粥样硬化性心脏病患者置入支架的特定人群和临床用药合理性等因素综合作用下,促进PCI后ISR发生。高频超声技术可以快速、无创测定血管内皮功能,间接反映冠状动脉受损情况,在PCI后ISR发生的风险因素评估中准确评价血管结构和功能变化,为临床治疗提供重要的诊断和治疗依据。     

早发冠心病患者的预后研究

目的研究早发冠心病患者经药物洗脱支架和(或)口服药物治疗后的近中期预后。方法经冠状动脉造影确诊的282例早发冠心病患者(男<55岁,女<65岁)按治疗方式的不同被分为早发冠心病介入治疗组(植入紫杉醇或雷帕霉素洗脱支架+药物治疗)177例和早发冠心病药物治疗组(单纯药物治疗)105例,分别对两组患者进行临床资料的收集比较和为期半年及一年的随访(包括主要心血管不良事件和冠心病的二级预防用药等)研究。结果早发冠心病介入治疗组的男性比例、以急性冠状动脉综合征方式起病的比例、多支病变比例、肌钙蛋白水平、住院天数及阿司匹林和氯吡格雷服用率均高于早发冠心病药物治疗组(P<0.05);与早发冠心病药物治疗组相比,早发冠心病介入治疗组的二级预防(包括二级预防用药的依从性及危险因素的控制)较好,但早发冠心病介入治疗组仍有较高的再发心绞痛和复合心血管不良事件的发生率(P<0.05)。Logistic回归分析显示,肥胖、急性冠状动脉综合征、减低的左心室射血分数可以预测早发冠心病患者在随访一年期间的复合心血管不良事件的发生。结论行药物洗脱支架植入联合药物治疗的早发冠心病患者须强化冠心病的二级预防。     

Psychosocial adjustment to coronary artery disease: current knowledge and future directions

Adjusting to the diagnosis of coronary artery disease can be a challenge to the coping abilities of patients and their families. To effectively support these clients' coping efforts, cardiovascular nurses must be knowledgeable about factors that affect the adjustment process. This article reviews recent findings regarding physiologic, psychologic, and sociodemographic influences on adjustment and presents a model that integrates these findings. Possible directions for further research are suggested.     

脉冲电磁场对原代大鼠骨髓来源内皮前体细胞生长及分化的影响

目的探讨脉冲电磁场对内皮前体细胞增殖及分化的影响。方法采用密度梯度离心法分离SD大鼠骨髓内皮前体细胞，将细胞分为对照组及磁场组。磁场组细胞于培养第5天后给予低频脉冲电磁场干预，直至培养终点。细胞增殖活性采用MTT法测定，用流式细胞仪检测Ⅷ因子相关抗原、NOS，表达阳性细胞。结果从磁场作用第5天开始，磁场组细胞增殖活性明显高于对照组；磁场作用第3天时，磁场组细胞Ⅷ因子相关抗原、NOS，表达阳性细胞数量均明显高于对照组，这种增高趋势持续至培养终点。结论低频脉冲电磁场可促进大鼠骨髓来源内皮前体细胞的增殖及分化。     

Echocardiography and coronary artery disease: Current and future applications

Echocardiographic techniques are becoming more widespread for evaluating patients with known or suspected coronary artery disease. Because it affords an excellent overall view of the heart, two-dimensional echocardiography, rather than M-mode echocardiography, is the imaging procedure of choice when dealing with coronary artery disease. This technique can be used to make the initial diagnosis of acute myocardial infarction, diagnose complications, and assess prognosis following myocardial infarction. Additionally by combining this test with stress testing, latent coronary artery disease can be detected. Recovery of wall motion can be assessed following interventions such as thrombolysis or balloon angioplasty. Investigational and future uses include tissue characterization, which may allow detection of ischemic but potentially viable myocardium, direct coronary visualization for detection of atherosclerotic involvement of the proximal coronary arteries and myocardial contrast echocardiography. The latter technique allows visualization of perfusion by way of injecting contrast material into the coronary circulation. This has been demonstrated to be an accurate means of determining myocardial infarction size in an animal model and is currently being used in a number of centers in patients at the time of cardiac catheterization. In summary two-dimensional echocardiography currently allows assessment of patients with myocardial infarction from the time of their presentation through their convalescent period with respect to diagnosis, prognosis and presence of complications. Exercise echocardiography can diagnose latent coronary artery disease. The newer investigational techniques show promise for furthering our ability to evaluate patients with coronary artery disease using echocardiography.     

二维应变超声心动图在冠心病诊断中的研究进展

二维应变超声心动图是定量评价心肌收缩和舒张功能的超声新技术,可计算组织运动的速度、应变、应变率、位移及旋转等参数。本文就二维应变超声心动图在冠心病应用的进展进行综述。