高血压患者血清尿酸与ADMA的关系

目的:研究原发性高血压患者血清尿酸与非对称性二甲基精氨酸(asymmetric dimethylarginine;ADMA)的关系.方法:检测原发性高血压合并高尿酸血症患者内皮系统ADMA 水平,并与单纯高血压组作对比,了解高尿酸对高血压患者内皮系统功能的影响,探讨高血压患者血清尿酸与内皮ADMA的关系.结果:高血压合并高尿酸血症组病人的血清ADMA水平高于单纯高血压组病人(P＜0.05);高血压病人的血清尿酸水平与ADMA呈正相关关系,r=0.713;P＜0.001;高血压患者ADMA与尿酸水平的多因素回归分析,尿酸是唯一有统计学意义的影响ADMA水平的自变量,其回归系数为0.002,P＜0.001.结论:本研究提示高血压患者血清尿酸水平与内皮ADMA呈正相关关系,高尿酸血症患者血清ADMA水平升高.     

中青年原发性高血压患者循环内皮祖细胞CD34+水平与颈动脉粥样硬化的相关性研究

目的 探讨中青年原发性高血压患者循环内皮祖细胞(EPCs)CD34+水平与颈动脉内膜中层厚度(IMT)和Framingham心血管危险因素积分标准(FRFC)的相关性及其评估高血压患者早期血管病变的价值.方法选择62例年龄25～45岁原发性高血压患者(高血压组)及20例健康体检者(健康对照组).高血压组患者采用FRFC分层方法分为低危组18例,中危组14例,高危组17例,极高危组13例.测定各组的外周循环EPCs CD34+水平及颈动脉IMT,并对EPCs CD34+水平与FRFC积分及颈动脉IMT进行相关性分析.结果 高血压各亚组患者外周循环EPCs CD34+水平随心血管危险程度的增加逐步下降[低危组(0.12±0.02)%,中危组(0.07±0.03)%,高危组(0.04±0.03)%,极高危组(0.01±0.01)%],各组间比较差异有统计学意义(P＜0.05或P＜0.01),且均明显低于健康对照组[(0.15±0.03)%,均P＜0.01];颈动脉IMT随心血管危险程度增加明显增厚[低危组(0.80±0.07)mm,中危组(1.11±0.08)mm,高危组(1.26±0.10)mm,极高危组(1.45±0.09)mm],各组间比较差异有统计学意义(P＜0.05或P＜0.01),且与健康对照组[(0.73±0.08)mm]比较差异有统计学意义(均P＜0.01).高血压患者外周循环EPCs CD34+水平与FRFC积分呈负相关(r=-0.875,P＜0.01),与颈动脉IMT呈负相关(r=-0.852,P＜0.01).结论 中青年原发性高血压患者循环EPCs CD34+水平与心血管危险因素及颈动脉IMT呈负相关;外周循环EPCs CD34+水平可以作为评估高血压患者早期血管病变的标志之一.     

脓毒症患者外周血祖细胞和内皮祖细胞数量的变化

目的 检测脓毒症患者外周血单个核细胞(peripheral blood mononuelear cell,PBMC)中祖细胞和血管内皮祖细胞(endothelial progenitor cells,EPC)相对数量的变化,探讨感染性休克和非休克患者外周血EPC变化的特点.方法 收集2007年8月至2008年2月复大学附属中山医院急诊科收治的脓毒症患者27例进行前瞻性研究,其中感染性休克患者12例、非休克患者15例,另选10例健康成年人作为正常对照,ICU非脓毒症患者10例作为ICU对照.Ficoll梯度离心法分离外周血PBMC,通过流式细胞仪检测外周血PBMC标记的CDl33,CIY34和血管内皮牛长因子受体-2(vascular endothelialgrowth factor receptor-2.VEGFR-2)的表达情况,计算祖细胞以及内皮祖细胞的相对数量.组间比较采用单因素方差分析.结果 健康成年人外周血祖细胞、EPC数量较少,分别占PBMC的0.25%.4-0.14%和0.09%.4-0.02%;ICU非脓毒症患者祖细胞和EPC数量分别占PBMC的0.38%.4-0.29%和0.12%.4-O.02%,与正常对照组相比无明显的变化(P>0.05);脓毒症非休克组患者外周血祖细胞、EPC的数量明显增加,分别占PBMC的0.57%±0.12%和0.22%±0.10%,与正常对照组相比差异具有统计学意义(P<0.05);感染性休克患者外周血祖细胞和EPE的数量明显减少,分别占PBMC的0.20%.4-0.12%和0.04%±O.01%,与非休克组、ICU对照组和正常对照组相比差异均具有统计学意义(P相似文献   

中青年原发性高血压患者循环内皮祖细胞CD34+水平与颈动脉粥样硬化的相关性研究

Objective To explore the relationship between the level of circulating endothelial progenitor cells (EPCs) CD34+with the Framingham cardiovascular risk factors, or with the carotid artery intima-madia thickness (IMT), and to evaluate the value of circulating EPCs CD34+level as a cytologicalmarker of early vascular lesion in youth and middle aged essential hypertension (EH) patients.Methods A total of 62 patients with EH aged between 25 to 45 were enrolled as study group and 20 healthy people were enrolled as control group.EH patients were stratified with cardiovascular risk factors according to Framingham risk factors score into low-risk group with 18 cases, mid-risk group with 14 cases, high-risk group with 17 cases, and extremely high-risk group with 13 cases.The level of circulating EPCs CD34+,carotid artery IMT were respectively measured.The relationship between the level of circulating EPCsCD34+ and Framingham cardiovascular risk factors score, carotid artery IMT was analyzed.Results The level of circulating EPCs CD34+ was gradually decreased with an increase of the Framingham risk factors score in each hypertensive subgroup [low-risk group:(0.12±0.02)%, mid-risk group:(0.07±0.03)%,high-risk group:(0.04±0.03)%, extremely high-risk group:(0.01±0.01)%], and they were significantly lower than that in control group [(0.15±0.03)%], and there was a significant difference among hypertensive subgroups (P＜0.05 or P＜0.01).Carotid artery IMT was significantly thicker among hypertensive subgroups [low-risk group:(0.80±0.07)mm, mid-risk group:(1.11±0.08)mm, high-risk group: (1.26±0.10)mm, extremely high-risk group:(1.45±0.09)mm], and there was a significant difference between each hypertensive group and that of control group [(0.73±0.08)mm, all P＜0.01].There was also statistical significance among hypertensive subgroups(P＜0.05 or P＜0.01).There was a negative correlation between the level of circulating EPCs CD34+and Framingham risk factors score (r=-0.875, P＜0.01), and also a negative correlation with carotid artery IMT (r=-0.852, P＜0.01).Conclusion There was a significant correlation between the level of circulating EPCs CD34+with Framingham risk factors score and also carotid artery IMT in EH patients.Circulating EPCs CD34+could be a cytological marker of early vascular lesion in hypertension patients.     

中青年原发性高血压患者循环内皮祖细胞CD34+水平与颈动脉粥样硬化的相关性研究

Objective To explore the relationship between the level of circulating endothelial progenitor cells (EPCs) CD34+with the Framingham cardiovascular risk factors, or with the carotid artery intima-madia thickness (IMT), and to evaluate the value of circulating EPCs CD34+level as a cytologicalmarker of early vascular lesion in youth and middle aged essential hypertension (EH) patients.Methods A total of 62 patients with EH aged between 25 to 45 were enrolled as study group and 20 healthy people were enrolled as control group.EH patients were stratified with cardiovascular risk factors according to Framingham risk factors score into low-risk group with 18 cases, mid-risk group with 14 cases, high-risk group with 17 cases, and extremely high-risk group with 13 cases.The level of circulating EPCs CD34+,carotid artery IMT were respectively measured.The relationship between the level of circulating EPCsCD34+ and Framingham cardiovascular risk factors score, carotid artery IMT was analyzed.Results The level of circulating EPCs CD34+ was gradually decreased with an increase of the Framingham risk factors score in each hypertensive subgroup [low-risk group:(0.12±0.02)%, mid-risk group:(0.07±0.03)%,high-risk group:(0.04±0.03)%, extremely high-risk group:(0.01±0.01)%], and they were significantly lower than that in control group [(0.15±0.03)%], and there was a significant difference among hypertensive subgroups (P＜0.05 or P＜0.01).Carotid artery IMT was significantly thicker among hypertensive subgroups [low-risk group:(0.80±0.07)mm, mid-risk group:(1.11±0.08)mm, high-risk group: (1.26±0.10)mm, extremely high-risk group:(1.45±0.09)mm], and there was a significant difference between each hypertensive group and that of control group [(0.73±0.08)mm, all P＜0.01].There was also statistical significance among hypertensive subgroups(P＜0.05 or P＜0.01).There was a negative correlation between the level of circulating EPCs CD34+and Framingham risk factors score (r=-0.875, P＜0.01), and also a negative correlation with carotid artery IMT (r=-0.852, P＜0.01).Conclusion There was a significant correlation between the level of circulating EPCs CD34+with Framingham risk factors score and also carotid artery IMT in EH patients.Circulating EPCs CD34+could be a cytological marker of early vascular lesion in hypertension patients.     

循环内皮祖细胞在阿托伐他汀钙干预肾性高血压大鼠体内的变化

背景:循环内皮祖细胞数量和功能降低预示高血压患者血管内皮修复能力降低,但有关他汀对高血压患者循环内皮祖细胞的影响尚不十分清楚.目的:血管内皮细胞及循环内皮祖细胞在阿托伐他汀钙干预肾性高血压大鼠体内的变化.设计、时间及地点:随机对照动物实验,2008-06/2009-02于重庆市神经病学重点实验室完成.材料:SPF级雄性SD大鼠24只,阿托伐他汀钙为辉瑞公司产品,批号:65837003.方法:随机抽取16只大鼠,应用经典的两肾一夹方法构建SD大鼠肾性高血压模型,随机分为高血压组、他汀组;剩余8只为对照组,行同样操作,但不套银夹.术后4周他汀组给予阿托伐他汀钙20mg/(kg·d)灌胃8周,其余两组大鼠给予等量蒸馏水灌胃8周.主要观察指标:实验第4,12周测各组大鼠血压、血脂,第12周通过苏木精-伊红染色观察胸主动脉内皮细胞层连续性,并测定循环内皮祖细胞数量及增殖、黏附和迁移能力.结果:他汀组第4,12周收缩压与同期模型组比较差异无显著性意义,但两组均明显高于同期对照组收缩压(P＜0.01);他汀组大鼠血脂无明显变化.模型组大鼠胸主动脉内皮层连续性严重受损;他汀组大鼠血管内皮细胞受损明显减轻.模型组循环内皮祖细胞数量显著低于他汀组与对照组,差异有显著性意义(P＜0.01);模型组循环内皮祖细胞增殖能力、黏附能力和迁移能力显著低于他汀组与对照组,他汀组仍低于对照组,3组之间比较差异有显著性意义(P＜0.01).结论:肾性高血压大鼠胸主动脉内皮细胞受损严重,循环内皮祖细胞数量及功能下降;阿托伐他汀钙可提高循环内皮祖细胞数量,改善循环内皮祖细胞功能.     

维持性血液透析患者循环内皮祖细胞变化的临床分析

目的 观察维持性血液透析患者循环内皮祖细胞(circulating endothelial progenitor cells,CEPCs)的变化.方法 以外周血中CD34+/CD133+/KDR + 为循环内皮祖细胞的标志物,对44例维持性血液透析患者和36例健康体检者采用流式细胞仪检测 CEPCs数量;将维持性血液透析患者的CEPCs数量与对照组比较,并根据维持性血液透析患者有无高血压或冠心病史、透析是否充分、血红蛋白水平进一步作亚组分析.结果维持性血液透析患者外周血CEPCs数量显著低于对照组( tCD34+=2.205,tCD34+/CD133+/KDR+ =2.148;均P＜0.05);合并高血压的维持性血液透析患者CEPCs数量较无高血压者显著降低(tCD34+ =2.183,tCD34+/CD133+/KDR+=2.023;均 P＜0.05);有冠心病史的维持性血液透析患者CEPCs数量低于无冠心病史者 (tCD34+=2.136,tCD34+/CD133+/KDR+ = 2.072;均P＜0.05);Kt/V≥1.3组患者CEPCs 数量明显高于Kt/V＜1.3组(tCD34+ =2.276,tCD34+/CD133+/KDR+=2.086;均 P＜0.05);血红蛋白≥110g/L组患者较血红蛋白＜110g/L组患者 CEPCs数量为高(tCD34+=2.707,t CD34+/CD133+/KDR+=2.859;均P＜0.05).结论 充分血液透析、积极控制高血压、改善肾性贫血使血红蛋白达标有助于提高维持性血液透析患者循环内皮祖细胞数量,有助于降低发生心血管并发症的风险.     

脓毒症大鼠循环内皮祖细胞的数量变化及其意义

目的 观察并分析脓毒症时循环内皮祖细胞(cEPCs)数量变化及其意义.方法 采用盲肠结扎穿孔术制备雄性SD大鼠脓毒症模型(80只),设正常对照组(16只)、假手术组(80只).于制模后即刻、6、12、18 h及1、2、3、7 d各组取9只大鼠,动态观察外周血单个核细胞(PBMCs)中cEPCs数(流式细胞学法)及血中肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、D-二聚体[酶联免疫吸附法(ELISA)]和抗凝血酶-Ⅲ(AT-Ⅲ,免疫浊度法)水平,肝、肾、肺组织湿/干重(W/D)比值.制模后1 d各组取8只大鼠,观察肝、肾、肺组织病理学变化及损伤评分.结果 制模后脓毒症大鼠cEPCs数量明显升高,于18 h达高峰[(7 161.9±689.8)个/106 PBMCs];血中TNF-α、IL-10、D-二聚体、AT-Ⅲ升高,分别于制模后12 h、12 h、3 d、18 h达峰值[(51.3±6.8) ng/L、(77.9±8.6) ng/L、(93.5±11.5) mg/L、(193.8±43.0) mg/L];肝、肾、肺W/D比值和组织损伤评分增加[18 h W/D比值:肝3.79±0.09,肾4.25±0.08,肺4.91±0.09;1 d组织损伤评分(分):肝1.86±0.26,肾5.14±0.34,肺6.57±0.37].模型组上述各指标均显著高于同期假手术组[18 h cEPCs数量(2 235.5±472.7)个/106 PBMCs,12 h TNF-α (14.3±5.8) ng/L,12 h IL-10 (35.0±5.8) ng/L,3 d D-二聚体(14.2±4.4) mg/L,18 h AT-Ⅲ (100.1±12.8) mg/L;18 h W/D比值:肝3.50±0.07,肾3.96±0.04,肺4.54±0.14;1 d组织损伤评分(分):肝0.29±0.18,肾0.57±0.20,肺1.14±0.51,P<0.05或P<0.01].相关分析显示,cEPCs数量与TNF-α(r=0.587)、IL-10(r=0.497)、D-二聚体(r=0.294)、AT-Ⅲ(r=0.690)及肝、肾、肺W/D比值(r1=0.532、r2=0.532、r3=0.679)均呈正相关(均P＜0.01).结论 脓毒症时cEPCs数量明显升高,其变化与炎症反应、凝血激活、毛细血管渗漏和组织损伤程度呈正相关.提示cEPCs数量增加是机体对脓毒症的反应,且数量变化可能代表炎症反应和内皮与组织损伤的程度.

Abstract：

Objective To observe the change in number of circulating endothelial progenitor cells (cEPCs) and analyze its significance in septic rat. Methods Septic model of male Sprague-Dawley (SD) rats was reproduced by cecum ligation and puncture (n=80), and the normal control group (n=16) and sham operation group (n=80) were established. Nine rats in each group were used, and the cEPCs numbers in peripheral blood mononuclear cells (PBMCs, by flow cytometry), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), D-dimer (by enzyme linked immunosorbent assay, ELISA), antithrombase-Ⅲ (AT-Ⅲ, by immunonephelometry), wet/dry (W/D) ratio of liver, kidney and lung were determined at 0, 6, 12, 18 hours and 1, 2, 3, 7 days after reproduction of model. Eight rats in each group were used, and the pathologic changes in liver, kidney and lung at 1 day were observed, and the injury scores were evaluated. Results The cEPCs number was markedly increased, reaching the peak [(7 161.9±689.8)/106 PBMCs] at 18 hours. Circulating TNF-α, IL-10, D-dimer, AT-Ⅲ were found to be increased, and the levels reached the peak at 12 hours, 12 hours, 3 days, 18 hours, respectively [(51.3±6.8) ng/L, (77.9±8.6) ng/L, (93.5±11.5) mg/L, (193.8±43.0) mg/L]. W/D ratio was elevated and signs of injury to the liver, kidney, lung became more obvious (18-hour W/D of liver: 3.79±0.09, kidney: 4.25±0.08, lung: 4.91±0.09; 1-day tissue evaluation of liver: 1.86±0.26, kidney: 5.14±0.34, lung: 6.57±0.37). The levels of all parameters in model group were significantly higher than those in sham operation group [18-hour cEPCs numbers: (2 235.5±472.7)/106 PBMCs, 12-hour TNF-α: (14.3±5.8) ng/L, 12-hour IL-10: (35.0±5.8) ng/L, 3-day D-dimer: (14.2±4.4) mg/L, 18-hour AT-Ⅲ: (100.1±12.8) mg/L; 18-hour liver W/D ratio: 3.50±0.07, kidney: 3.96±0.04, lung: 4.54±0.14; 1-day tissue evaluation of liver: 0.29±0.18, kidney: 0.57±0.20, lung: 1.14±0.51, P<0.05 or P<0.01]. There was positive correlation between cEPCs numbers and TNF-α (r=0.587), IL-10 (r=0.497), D-dimer (r=0.294), AT-Ⅲ (r=0.690), and W/D ratio of liver, kidney, lung (r1=0.532, r2=0.532, r3=0.679, all P<0.01). Conclusion The cEPCs number markedly increases in septic rats, and it shows positive correlation with the degree of inflammatory reaction, blood clotting activation, capillary leakage and tissue damage. The increase of number of cEPCs is the result of reaction to sepsis, and its change in number might be valuable in evaluating the pathogenesis of sepsis.     

原发性高血压患者左室构型与外周血管内皮功能障碍之间的关系

目的　探讨原发性高血压( EH)患者左室构型( L VG)与外周内皮功能障碍之间的关系。方法　超声观察5 5例EH患者和2 0例正常人的心脏结构功能,采用高频超声研究受检者的肱动脉充血后反应性扩张( DIRH)和含服硝酸甘油后血管内径的变化( DING)。结果　( 1 )与正常组( 1 3 .0 9%±3 .3 5 % )相比,左室正常构型组、向心性重构组的DIRH( 8.4 3 %±1 .71 % ;7.94 %±1 .5 7% )均显著减小( P<0 .0 0 1 ) ,而后2组间的DIRH、3组间的DING无显著性差异( P>0 .0 5 ) ;( 2 )左室向心性肥厚组、离心性肥厚组的DIRH ( 3 .2 0 %±1 .72 % ;5 .81 %±1 .72 % )较正常构型组、向心性重构组显著减小,且向心性肥厚组最为显著( P<0 .0 0 1 ) ;( 3 )除左室离心性肥厚组患者的EF( 5 3 .5 5 %±3 .1 2 % )、FS( 3 0 .3 3 %±9.4 % )较正常组( 6 0 .95 %±6 .0 3 % ;3 5 .80 %±5 .72 % )显著减小( P<0 .0 0 1 )外,其余患者EF、FS与正常组间无显著性差异;( 4 )不同左室构型组患者的血压较正常组显著增高,但各组患者之间无显著性差异( P>0 .0 5 )。各组患者的年龄、血糖、血胆固醇及血甘油三脂均与正常组间无显著性差异( P>0 .0 5 )。结论　不同左室构型的EH患者的外周血管内皮功能障碍程度不同,血管内皮功能障碍可能是影响左室构型     

非对称性二甲基精氨酸和肿瘤坏死因子对原发性高血压左心室构型的影响

目的 观测正常人及高血压患者在不同左心室构型组血清中的肿瘤坏死因子α(TNF-α)和非对称性二甲基精氨酸(ADMA)浓度变化,并探讨TNF-α和ADMA在高血压心脏损害中的病理生理作用.方法 选取体检健康人员30名为正常对照组.轻中度高血压患者66例,根据左心室质量指数(LVMI)和相对室壁厚度(RWT)将其分为4组,即正常左心室构型组:LVMI和RWT均正常;向心性构型组:LVMI正常,RWT增大;向心性肥厚型组:LVMI和RWT均增大;离心性肥厚型组:LVMI增大,RWT正常.采用放射免疫法及反相高效液相色谱法分别测定各组血清中TNF-α及ADMA.结果 对照组和以上4组中TNF-α分别为(11.86±2.45)、(22.08±4.67)、(25.88.4±5.36)、(32.54±5.63)、(48.72±8.86)ng/L;ADMA:(0.78±0.22)、(1.32±0.18)、(1.87±0.20)、(3.03±0.14)、(4.11±0.17)p.mol/L.血清TNF-α和ADMA水平随左心室构型严重程度的增加而升高,左心室构型组患者均明显高于正常对照组(P均<0.01),且左心室重构各亚组间两两比较差异均有统计学意义(P均<0.01).结论 TNF-α和ADMA可能参与了高血压左心室构型的发生和发展.     

盐敏感性高血压患者血清非对称二甲基精氨酸的测定及临床意义

目的检测盐敏感性高血压患者血清非对称二甲基精氨酸(ADMA)水平并探讨临床意义。方法选择68例盐敏感性高血压患者为观察组研究对象,选择60例健康体检者为对照组。检测两组血清ADMA、一氧化氮(NO)、血脂,并比较观察组不同高血压分级患者血清ADMA水平的差异。采用Pearson相关分析对ADMA与其它危险因素的相关性进行分析。结果观察组ADMA、NO水平显著高于对照组(P<0.05);随着观察组患者高血压分级的升高,患者血清ADMA水平逐渐上升,差异具有统计学意义(P<0.05);ADMA水平与患者NO水平、收缩压(SBP)及脉压差(PP)显著相关,与血脂水平无显著相关(P>0.05)。结论 ADMA参与盐敏感性高血压的发生和发展,其机制可能是通过影响血管内皮功能,加强对ADMA的监测对于评估病情、指导治疗具有重要意义。     

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.     

The role of asymmetric dimethylarginine (ADMA) and leptin in hypertensive patients

We investigated the role of leptin and asymmetric dimethylarginine (ADMA) in uncomplicated hypertension. We also investigated their relationship with insulin resistance and serum levels of several metabolic parameters, including homocysteine, lipoprotein(a) and malondialdehyde (MDA). A total of 34 untreated newly-diagnosed hypertensive patients (seven men and 27 women; mean age, 57.4 +/- 10.1 years) and 38 normotensive healthy subjects (20 men and 18 women; mean age, 55.9 +/- 8.7 years) were studied prospectively. Serum leptin, homocysteine, lipoprotein(a), MDA and insulin resistance (HOMA-IR) were significantly higher in hypertensive patients compared with normotensive subjects. There were no significant differences in ADMA, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 between the two groups. No correlation was found between serum ADMA and leptin levels. Our findings suggest that high serum leptin and homocysteine levels, oxidative stress and insulin resistance may be important risk factors for atherosclerosis among patients with uncomplicated hypertension.     

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。     

系统性硬皮病患者外周血内皮祖细胞数量及分化功能的研究

目的探讨系统性硬皮病（Systemic scleroderma,SSc）患者外周血内皮祖细胞（endothelial progenitor cells,EPCs）数量和分化功能的变化。方法选取女性SSc患者及健康志愿者各20例,抽取外周血20 ml,密度梯度离心法分离单个核细胞,以CD133/CD34、CD133/VEGFR2双荧光标记鉴定细胞,CD34/CD133/VEGFR2三荧光标记流式检测EPCs数量;分别以PE标记抗人CD14,FITC标记抗人CD64,PerCP/Cy5.5标记抗人VEGFR2,流式细胞仪检测单阳性细胞率,进而比较分化功能。结果 SSc患者外周血EPCs表达阳性率（3.18±1.97）%,较健康对照的（20.56±4.37）%明显下降,差异有统计学意义（P〈0.01）;培养7天后,外周血单个核细胞表达单核细胞表面标志CD14＋、CD64＋细胞百分率（32.49±5.41）%、（30.57±4.83）%,与对照组的（14.76±2.37）%、（15.39±2.09）%比较明显增加,差异均有统计学意义（均P〈0.01）,而内皮细胞表面标记KDR＋细胞百分率（68.38±4.65）%与对照组的（89.81±5.13）%比较明显减低,差异有统计学意义（P〈0.01）。结论 SSc患者循环内皮祖细胞数量减少,分化功能降低。     

低体重早产儿内皮祖细胞体外血管生成能力研究

目的：探讨低体重早产儿的内皮祖细胞（endothelial progenitor cells, EPCs）血管生成能力及调控机制。方法：收集15例低体重早产儿（胎龄小于37周且体重小于 2.5 kg）和19例对照足月儿（胎龄大于37周且体重大于等于2.5 kg）的脐带血,于诱导分化前用流式细胞仪检测EPCs（CD34⁺/CD133⁺/VEGFR2⁺）的数量。分离培养后,检测EPCs克隆形成时间、克隆形成能力、细胞增殖能力和小管形成能力。用蛋白印迹法检测EPCs中血管内皮钙粘蛋白（vascular endothelial cadherin,VE-cadherin）和血管内皮生长因子受体2（vascular endothelial growth factor receptors 2,VEGFR2）的表达情况。结果：与足月儿相比（0.003%±0.002%）,低体重早产儿脐带血中的EPCs百分比（0.0026%±0.0025%）并无变化,但EPCs克隆形成时间推迟（18 d比12 d）,克隆形成能力、细胞增殖能力及小管形成能力均较足月儿下降（P均<0.05）。蛋白印迹法检测结果显示,低体重早产儿脐带血EPCs中的VE-cadherin和VEGFR2表达降低。结论：低体重早产儿的EPCs血管生成能力受损,可能与EPCs中血管内皮特异性标志物VE-cadherin、VEGFR2表达降低有关。     

Improving cardiovascular outcomes in rheumatic diseases: Therapeutic potential of circulating endothelial progenitor cells

Patients with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). The reason for this is unclear but may be due, at least in part, to the failure of endothelial repair mechanisms. Over the last 15 years there has been much interest in the mechanisms of endothelial renewal and its potential as a therapy for CVD. In the circulation there are two distinct populations of cells; myeloid angiogenic cells (MACs) which augment repair by the paracrine secretion of angiogenic factors, and outgrowth endothelial cells (OECs) which are true endothelial progenitor cells (EPCs) and promote vasculogenesis by differentiating into mature endothelium. There are marked abnormalities in the number and function of these cells in patients with RA and SLE. Inflammatory cytokines including interferon-alpha (IFNα) and tumour-necrosis factor alpha (TNFα) both impair MAC and OEC function ex vivo and may therefore contribute to the CVD risk in these patients. Whilst administration of mononuclear cells, MACs and other progenitors has improved cardiovascular outcomes in the acute setting, this is not a viable option in chronic disease. The pharmacological manipulation of MAC/OEC function in vivo however has the potential to significantly improve endothelial repair and thus reduce CVD in this high risk population.