血管内皮细胞钙离子浓度与缺氧及血管紧张素Ⅱ的相关性

目的 观察缺氧及血管紧张素Ⅱ(AngⅡ)对血管内皮细胞(VEC)内钙离子浓度的影响.方法 建立VEC缺氧损伤模型;实验设为对照组、缺氧组、AngⅡ作用组、缺氧+AngⅡ作用组共4组.各组细胞经过F1uo-3/AM负载后,用激光共聚焦显微镜测定VEC内Fluo-3的荧光强度代表钙离子浓度.结果 VEC分别经过缺氧及AngⅡ损伤后,细胞内钙离子浓度明显升高(P＜0.01);缺氧条件下AngⅡ可引起VEC钙离子浓度进一步升高(P＜0.05).结论 缺氧及AngⅡ可引起VEC内钙离子浓度明显升高,造成VEC损伤.     

性激素水平及平衡对大鼠血管内皮细胞增殖的调节作用及意义

目的　探讨雌、雄及孕激素分别对雌、雄性大鼠肺血管内皮细胞 (VEC)增殖的影响。方法　采用组织贴块法培养大鼠肺血管内皮细胞 ,应用噻唑蓝 (MTT)比色法检测大鼠VEC的增殖情况。结果　 (1) 3× 10 -8mol/L、3×10 -7mol/L 17 β雌二醇 (E2 )可促进雌鼠肺VEC的增殖 (P <0 .0 1) ;3× 10 -9mol/L、3× 10 -8mol/L、3× 10 -7mol/L 17 βE2 均能促进雄鼠VEC的增殖 (P<0 .0 5 ) ,各组间无明显差异。雌激素受体拮抗剂他莫昔芬可阻断 17 βE2 上述促增殖作用。 (2 ) 3× 10 -8mol/L、3× 10 -7mol/L睾酮 (T)均可明显促进雄鼠VEC的增殖(P <0 .0 5 ) ,但对雌鼠VEC增殖无促进作用。 (3)E2 /孕激素 (P) =3/ 10时能促进雌鼠VEC的增殖 (P<0 .0 5 )。(4)E2 /T =1亦可促进雌鼠VEC增殖 (P<0 .0 5 )。结论　雌激素可促进雌、雄性大鼠VEC的增殖 ,其促增殖作用无性别差异 ,且通过雌激素受体 (ER)介导。雄激素仅可促进雄性大鼠VEC增殖 ,单纯孕激素对雌鼠VEC增殖无明显影响。E2 /T、E2 /P比值的平衡对雌鼠VEC的增殖也起重要作用     

原人参二醇对胃癌诱导血管内皮细胞增殖的抑制作用

目的 探讨原人参二醇(Ppd)对胃癌诱导血管内皮细胞(VEC) 增殖的抑制作用.方法 采用MTT 法检测不同浓度Ppd对VEC、人胃癌SGC-7901 细胞增殖及SGC-7901细胞诱导VEC增殖的影响.结果 Ppd对VEC、人胃癌SGC-7901 细胞生长有明显的抑制作用,且呈量效关系,IC_(50)为2.0 μg/ ml,且肿瘤细胞产生明显的G_1期阻滞现象,Ppd为2.0 μg/ml时,G_1细胞百分率达76.08%,而在Ppd为10.0 μg/ml时为81.17%,较对照组39.02%明显增多(P<0.05),而S期、G2+M期细胞数明显减少.Ppd浓度为2.0 μg/ml时,对SGC-7901细胞条件培养液诱导的VEC增殖有抑制作用(P< 0.01),抑制率为13.10 %～77.38 %.结论 Ppd对胃癌细胞条件培养液诱导的VEC 增殖具有抑制作用.     

血管内皮生长因子预防血管成形术后再狭窄的机制研究

目的:探讨血管内皮生长因子(VEGF)预防血管成形术后再狭窄的机制.方法:用高脂饲养建立实验性动脉粥样硬化家兔模型,将VEGF作用于正常健康兔和动脉粥样硬化家兔主动脉血管内皮细胞(VEC).采用亚硝酸还原法测一氧化氮(NO),放免法测内皮素(ET)、6-酮-前列腺素1α( 6-keto-PGF1α),采用发色底物显色法测定血浆纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制物-1(PAI-1)活性.并用WST-1比色法观察VEGF对上述VEC增殖的影响.结果:与空白对照组(VEGF 0 μg/L)比较, 10 μg/L、20 μg/L VEGF处理组NO、6-keto-PGF1α、PAI均明显增加,而ET、t-PA、t-PA/PAI均明显降低,并呈剂量依赖性.与正常健康兔VEC(正常VEC)比较,动脉粥样硬化家兔VEC(异常VEC)分泌ET、PAI、t-PA均明显增加,而NO、6-keto-PGF1α、t-PA/PAI均明显降低.结论:动脉粥样硬化家兔伴有内皮功能异常,而VEGF能促进正常和异常VEC的增殖并分泌NO、PGI2、PAI,而抑制ET、t-PA的分泌,使t-PA/PAI降低.     

血管内皮细胞与心血管疾病的关系及其研究进展

血管内皮细胞 ( VEC)为衬贴于血管内腔面的单层扁平细胞 ,其表面积可达 1 0 0 0 m2以上。VEC分泌多种调节血管功能的活性物质 ,与心血管疾病有密切关系。最近已有研究试图通过干预治疗以恢复某些心血管疾病患者的内皮功能 ,改善预后 ,这是心血管疾病治疗方法中新的探索。现就 VEC与心血管疾病的关系及其研究进展作一简要综述。1　血管内皮细胞合成与释放的血管活性物质1 .1　 VEC合成与释放的缩血管活性物质　 VEC合成与释放的缩血管活性物质包括内皮素 ( ET)、内皮依赖性收缩因子 ( EDCF)、前列腺素 H2 ( PGH2 )、血栓素 A2 ( T…     

预处理对在体大鼠冠脉血管内皮细胞的保护及机制探讨

.01).IPC能逆转上述改变,使血浆中NO增多,ET降低,NO/ET值恢复,CEC数量减少,MDA含量降低(P<0.05或P<0.01).PKC的抑制剂多黏菌素B并不加重I/R的上述改变,但是能阻断IPC的作用.电镜显示:I/R后VEC的超微结构严重损伤,IPC能明显减轻VEC的结构损伤.结论 I/R导致VEC结构和功能的严重损伤,IPC能减轻I/R后VEC的结构和功能损伤,PKC可能参与了这一过程.     

中药对血管内皮细胞功能的影响

通过对中药影响血管内皮细胞（VEC）的屏障、感受、分泌、损伤修复以及肿瘤性增殖等几个方面进行综述,研究中药对VEC的作用,揭示中医药作用于神经内分泌免疫网络（NEIN）的机制.     

中医药保护血管内皮细胞作用机制的研究进展

血管内皮细胞(vascular endothelial cell,VEC)不仅是血流和血管壁之间的机械屏障,而且是高度活化的、功能异常活跃的内分泌、旁分泌及代谢器官,多种理化因素可导致内皮细胞功能障碍,成为血管性疾病产生的关键环节[1],中医药具有明显的保护VEC的作用,现将近年研究概况综述如下.     

血管内皮细胞功能损伤机制的研究进展

血管内皮细胞(VEC)作为血管腔内的一层特化细胞,是血液和组织之间的关键调控界面,因此也成为了多种血管损伤因素的潜在靶点。VEC损伤是多种慢性疾病的共同生理变化,也是包括动脉硬化在内的多种心血管疾病的初始发病机制,其具体机制尚有待进一步阐明。探究VEC损伤的普遍病理机制有助于改善心血管疾病的发展和预后。文章主要就血管活性物质、炎症反应、氧化应激、凝血系统及其他因素等引起VEC损伤的普遍损伤机制进行综述。     

血管内皮细胞衰老与心血管疾病的相关性

血管内皮细胞(VEC)是覆盖于血管内膜表面的单层扁平鳞状上皮细胞,其构成血管壁的生物屏障,不仅属于一种保护性屏障,还能够产生一些自体分泌物用于调节体内平衡和血管紧张度。VEC衰老可导致血管功能受损,是心血管系统(CVS)主要的危险因素,并与心血管疾病(CVD)有着密切的关系。然而,VEC衰老的机制以及VEC衰老对血管功能的影响尚不完全清楚。本综述总结了VEC衰老的特征及其相关分子机制,并对年龄相关CVD进行了阐述。     

血管内皮细胞和原发性高血压

原发性高血压是常见的心血管疾病,其发病机制目前仍不明确。随着对血管内皮细胞的深入研究,发现原发性高血压的发生和血管内皮细胞有密切的关系。现从血管内皮细胞的生物学特性以及与原发性高血压的关系研究现状作一综述。     

Modulation of RAGE expression influences the adhesion of red blood cells from diabetic patients

Atherothrombotic complications are frequent in patients with type 2 diabetes. Red blood cells (RBC) from diabetic patients exhibited an increased adhesion which correlated to the extent of vascular complications. In the present study we have investigated the adhesive interactions of RBCs with endothelium, using flow-based assessments. RBCs and endothelial cells were unstimulated or stimulated using respectively adrenaline and TNFalpha. Adhesion assays were carried-out by drawing the RBC suspension through a glass microcapillary tube precoated by human umbilical vein endothelial cells. These microslides were then incorporated into a controlled flow system equipped with a computerized video-microscopic image analysis. RBCs from diabetic patients bind to endothelial cells and could withstand wall shear stresses above 0.1 Pa. After stimulation by TNFalpha the adhesion was 1.5-fold higher. Blocking experiments demonstrated that the adhesion was mediated by the receptor for AGE (RAGE). Adrenaline-treated RBCs showed a transient increase in adhesion at low shear stresses. Inflammatory mediators or catecholamine amplifying diabetic RBC adhesion may aggravate endothelial cell damages.     

Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.

Vascular endothelial cell growth factor, a mitogen selective for vascular endothelial cells in vitro that promotes angiogenesis in vivo, functions through distinct membrane-spanning tyrosine kinase receptors. The cDNA encoding a soluble truncated form of one such receptor, fms-like tyrosine kinase receptor, has been cloned from a human vascular endothelial cell library. The mRNA coding region distinctive to this cDNA has been confirmed to be present in vascular endothelial cells. Soluble fms-like tyrosine kinase receptor mRNA, generated by alternative splicing of the same pre-mRNA used to produce the full-length membrane-spanning receptor, encodes the six N-terminal immunoglobulin-like extracellular ligand-binding domains but does not encode the last such domain, transmembrane-spanning region, and intracellular tyrosine kinase domains. The recombinant soluble human receptor binds vascular endothelial cell growth factor with high affinity and inhibits its mitogenic activity for vascular endothelial cells; thus this soluble receptor could act as an efficient specific antagonist of vascular endothelial cell growth factor in vivo.     

Pathological aging of the vascular endothelium: are endothelial progenitor cells the sentinels of the cardiovascular system?

Aging is associated with vascular endothelial dysfunction, which ultimately leads to atherosclerosis. On the other hand, it is clear that in young patients with risk factors for cardiovascular diseases (CVD), endothelial dysfunction is an early marker of the ongoing atherogenic process. It is therefore tempting to speculate that risk factors for CVD accelerate the aging process. The aging of an endothelial cell (EC) is not chronological but rather dependent on its replication rate. ECs have a finite number of divisions and enter replicative senescence after exhaustion of this potential. Telomere attrition is believed to be responsible for this phenomenon. Upon reaching a critical minimal telomere length, ECs enter a nondividing state of replicative senescence. Recently, endothelial progenitor cells originating from the bone marrow have been isolated from the circulation. They integrate into the endothelial layer of the vessel and contribute to healing, ischemic repair and angiogenesis. A completely new field of investigation is now open. Are endothelial progenitor cells sensitive to the aging process? Do they prevent endothelial dysfunction? Are they the ultimate shield against the damages induced by risk factors for CVD? There are no definite answers to these questions, but the potential of these cells is tremendous and understanding their physiology is essential.     

内皮细胞凋亡与肺动脉高压

随着肺动脉高压研究的不断深入,肺血管内皮细胞凋亡在肺动脉高压形成过程中的重要作用被逐步认识。多种疾病和环境因素导致肺血管内皮损伤、内皮细胞凋亡增加、功能障碍,从而促进肺动脉平滑肌细胞和成纤维细胞增殖、肺动脉重构和血栓形成;肺血管内皮细胞凋亡还诱导产生凋亡抵抗表型的内皮细胞过度增殖,形成丛样病变和肺血管闭塞,最终导致严重肺动脉高压。因而在肺动脉高压发生发展的不同时期,调控肺血管内皮细胞凋亡可能是预防和治疗肺动脉高压的一种新策略。     

急性冠状动脉综合征病人VEGF与VCAM-1水平及其与斑块稳定性的研究

目的观察急性冠状动脉综合征病人血清血管内皮生长因子(VEGF)和血管细胞黏附分子-1(VCAM-1)等指标的水平,探讨两者与斑块稳定性的关系及其临床意义.方法根据临床诊断将研究对象分为急性冠状动脉综合征组(ACS组,30例)和稳定劳累性心绞痛组(SAP组,25例),另设健康对照组(30名),测定上述观测者入院血清VEGF、VCAM-1、肌酸激酶(CK)及其同工酶(CK-MB)的水平.结果 ACS组病人血清VEGF、VCAM-1、CK﹑CK-MB水平均显著高于SAP组和健康对照组.血清VEGF的水平与血清VCAM-1水平和CK-MB水平之间有相关性(r＝0.233,P＜0.05;r＝0.547,P＜0.01),与CK水平之间无相关性(r＝-0.139,P>0.05).结论急性冠状动脉综合征的早期VEGF和VCAM-1血管水平明显升高,对判定斑块稳定性具有一定价值.     

Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division

Mice lacking the vascular endothelial growth factor (VEGF) receptor flt-1 die of vascular overgrowth, and we are interested in how flt-1 normally prevents this outcome. Our results support a model whereby aberrant endothelial cell division is the cellular mechanism resulting in vascular overgrowth, and they suggest that VEGF-dependent endothelial cell division is normally finely modulated by flt-1 to produce blood vessels. Flt-1(-/-) embryonic stem cell cultures had a 2-fold increase in endothelial cells by day 8, and the endothelial cell mitotic index was significantly elevated before day 8. Flt-1 mutant embryos also had an increased endothelial cell mitotic index, indicating that aberrant endothelial cell division occurs in vivo in the absence of flt-1. The flt-1 mutant vasculature of the cultures was partially rescued by mitomycin C treatment, consistent with a cell division defect in the mutant background. Analysis of cultures at earlier time points showed no significant differences until day 5, when flt-1 mutant cultures had increased beta-galactosidase(+) cells, indicating that the expansion of flt-1 responsive cells occurs after day 4. Mitomycin C treatment blocked this early expansion, suggesting that aberrant division of angioblasts and/or endothelial cells is a hallmark of the flt-1 mutant phenotype throughout vascular development. Consistent with this model is the finding that expansion of platelet and endothelial cell adhesion molecule(+) and VE-cadherin(+) vascular cells in the flt-1 mutant background first occurs between day 5 and day 6. Taken together, these data show that flt-1 normally modulates vascular growth by controlling the rate of endothelial cell division both in vitro and in vivo.     

7-二氟甲氧基金雀异黄素对H_2O_2诱导血管内皮细胞与单核细胞黏附的抑制作用

目的 探讨7-二氟甲氧基金雀异黄素对氧化应激诱导血管内皮细胞与单核细胞黏附的抑制作用及其机制.方法 荧光分光光度计检测单核细胞与血管内皮细胞的黏附,酶联免疫吸附法检测E选择素和细胞间黏附分子1等黏附分子的释放,Western blotting检测P38丝裂原活化蛋白激酶的磷酸化水平.结果 H2O2处理血管内皮细胞24 h后,内皮细胞-单核细胞的黏附率显著增加,内皮细胞E选择素和细胞间黏附分子1的释放增加;加入7-二氟甲氧基金雀异黄素后,血管内皮细胞-单核细胞的黏附率以及内皮细胞释放E选择素和细胞间黏附分子1等黏附分子呈浓度依赖性减少.H2O2处理血管内皮细胞24 h后,可显著激活P38丝裂原活化蛋白激酶,这一作用可被7-二氟甲氧基金雀异黄素所抑制.给予P38丝裂原活化蛋白激酶特异性抑制荆SB203580亦可阻断H2O2诱导的内皮细胞-单核细胞黏附及内皮细胞E选择素和细胞间黏附分子1的释放.结论 7-二氟甲氧基金雀异黄素对氧化应激诱导的血管内皮细胞与单核细胞黏附具有拮抗作用,其机制可能与其抑制P38丝裂原活化蛋白激酶的激活进而阻断内皮细胞释放黏附分子E选择素和细胞间黏附分子1有关.     

Effect of serum from patients with idiopathic thrombocytopenic purpura on cultured endothelial cell growth

This study examined the effects of platelet-derived serum factors from patients with idiopathic thrombocytopenic purpura (ITP) on human umbilical cord vascular endothelial cell growth and DNA synthesis. Vascular endothelial cell growth factors were identified in the platelet extracts, and platelet-derived vascular endothelial cell growth factors with molecular weights of less than 10,000 were also identified in the sera. These growth factors were stable even after 30 minutes of heat treatment at 56 degrees C and acid treatment. When ITP patient serum was added to vascular endothelial cells, their growth capacity and DNA synthesis capacity were lower than when serum from normal subjects or patients with ITP in remission was added. This indicated that in ITP, impairment of vascular integrity and abnormal repair of the vascular walls that accompany thrombocytopenia may be causes of the predisposition to hemorrhage. The decrease in ITP of platelet-derived vascular endothelial cell growth factors with molecular weights of less than 10,000 was hypothesized to be a contributory factor.     

僵蚕抗凝血酶诱导血管内皮细胞释放作用的研究

目的研究僵蚕抗凝血酶诱导血管内皮细胞释放作用的影响。方法将不同浓度的僵蚕注射液（600μg/mL,300μg/mL,150μg/mL）加入凝血酶诱导的血管内皮细胞中,培养12h后收集细胞液,观察不同浓度的僵蚕注射液对凝血酶诱导血管内皮细胞释放作用的影响。结果僵蚕大、中、小剂量组较凝血酶组均能明显增加组织型纤溶酶原激活物（t-PA）活性,分别为（0.460±0.010）U/mL,（0.457±0.019）U/mL,（0.366±0.014）U/mL（P〈0.01）;同时也可降低纤溶酶原活化素抑制物（PAI）活性,降低血管性假血友病因子（vWF）含量,与凝血酶组比较差异具有统计学意义（P〈0.01）。结论僵蚕注射液可以明显抑制凝血酶诱导的内皮细胞释放作用,此作用与僵蚕的抗凝作用有关。