血管内皮生长因子对OX-LDL诱导的内皮细胞凋亡的影响及其机理

目的研究血管内皮生长因子（VEGF）对氧化型低密度脂蛋白（OX—LDL）诱导的血管内皮细胞凋亡的拮抗作用及其机理，以探讨VEGF预防血管成形术后再狭窄的机制。方法将对数生长期的人脐静脉内皮细胞分成对照组、OX—LDL处理组和OX—LDL＋VEGF处理组，12h后采用原位末端标记法和流式细胞术观察各组细胞的凋亡发生情况，并通过逆转录聚合酶链反应研究各组细胞中凋亡相关基因Bcl-2与Fas mRNA的表达情况。结果OX—LDL处理组凋亡细胞和Fas mRNA表达明显多于对照组和OX-LDL＋VEGF处理组，而Bcl-2 mRNA表达情况相反。结论VEGF能部分拮抗OX—LDL诱导的血管内皮细胞凋亡，可能与其上调Bcl-2 mRNA表达及下调Fas mRNA表达有关，为VEGF预防血管成形术后再狭窄进一步提供了理论依据。     

血管内皮细胞生长因子与实体肿瘤

血管内皮细胞生长因子（ＶＥＧＦ）具有选择性促血管内皮细胞生长和增强血管渗透性的作用，在多种实体肿瘤中有高水平合成，并与肿瘤的分级和转移相关，ＶＥＧＦ受体主要表达于血管内皮细胞，通过干预ＶＥＧＦ及其受体抑制肿瘤血管形成是阻遏肿瘤生长和转移的重要策略     

VEGF基因对缺氧诱导的内皮细胞凋亡和坏死的影响

采用缺氧诱导体外培养血管内皮细胞凋亡模型, 用脂质体介导的基因转移法将含血管内皮生长因子(VEGF)cDNA的真核表达载体pSVI21 导入血管平滑肌细胞(VSMC) 中, 取此VSMC条件培养液, 再行血管内皮细胞(VEC) 培养, 用透射电镜、原位末端标记和流式细胞仪分析法观察VEGF对凋亡产生的影响。结果发现: 缺氧组凋亡发生率明显增加, 而加用转基因VSMC条件培养液后凋亡发生率明显减少, 并可减轻缺氧致内皮细胞超微结构的改变。结果表明: VEGF可减少缺氧诱导血管内皮细胞凋亡的产生, 保持血管内皮细胞的完整, 有益于防止或减少缺氧时内皮受损及内皮功能紊乱     

KDR反义寡核苷酸对人血管内皮细胞的作用

VEGF及其受体KDR在肿瘤血管生成中起重要作用。我们用KDR特异性反义寡核苷酸作用于人血管内皮细胞，以阻断VEGF的自分泌作用通路，观察对细胞增殖的影响、细胞超微结构的变化及检测细胞DNA含量，测定细胞分泌VEGF的能力，并检测作用后KDR mRNA和KDR蛋白的水平。结果发现未经处理的人血管内皮细胞能分泌一定量的VEGF，KDR ASODN能抑制人血管内皮细胞内KDR基因的表达，并显著抑制细胞的增殖，在一定剂量下还可诱导凋亡。结果说明KDR ASODN能显著抑制血管内皮细胞的增殖，VEGF受体KDR在人血管内皮细胞的增殖和凋亡的凋控中起重要作用。     

可溶性血管内皮生长因子受体1真核克隆表达及其对血管内皮细胞增殖的影响

本研究旨在构建可溶性血管内皮生长因子(vascular endothelial growth factor,VEGF)受体1(soluble fmslike tyosine kinase-1,sFlt-1)的真核表达质粒pcDNA3.1-sFlt-1,并观察sFlt-1对血管内皮细胞增殖的影响。提取人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)总RNA,扩增Flt-1基因胞外1-3结构域,构建真核表达质粒pcDNA3.1-sFlt-1,测序鉴定基因序列。将重组质粒转染Lewis肺癌细胞,采用RT-PCR和SDS-PAGE检测sFlt-1在基因及蛋白水平的表达情况。MTT法检测sFlt-1对VEGF诱导的HUVECs生长的影响。结果显示:①插入片段序列正确;②sFlt-1在基因水平成功表达且转染后的Lewis肺癌细胞能分泌表达sFlt-1;③含sFlt-1的细胞上清液可明显抑制VEGF诱导的HUVECs增殖。本研究成功构建了真核表达质粒pcDNA3.1-sFlt-1,sFlt-1,在基因和蛋白水平均获得有效表达,且表达的蛋白可明显抑制由VEGF诱导...     

血管内皮细胞生长因子受体KDR胞外配基结合区单抗对内皮细胞增殖及血管形成的抑制

目的　研制能封闭血管内皮生长因子 (VEGF)受体KDR的单克隆抗体 (McAb) ,探讨其抑制VEGF诱导的体内外活性。方法　以原核表达的KDRⅠ～Ⅳ区融合蛋白免疫BALB/c小鼠 ,用杂交瘤技术制备抗KDRⅠ～Ⅳ的McAb ,并用免疫双扩、ELISA和Western免疫印迹鉴定其亚类和抗原结合特异性 ,用VEGF刺激内皮细胞增殖及鸡胚血管形成实验检测该抗体的中和活性。结果　通过筛选和鉴定获得了 2株KDRⅠ～Ⅳ区McAbs(3G9、1E4) ,其分泌抗体亚类分别为IgG1和IgM。 2株McAb均能明显抑制VEGF诱导的内皮细胞 (EC)增殖 ,经纯化的McAb 3G9能明显抑制经VEGF刺激的鸡胚血管形成。结论　KDRⅠ～Ⅳ区McAb可能通过封闭内源性KDR而抑制VEGF活性 ,McAb 3G9具有潜在治疗肿瘤的应用前景。     

血管内皮细胞生长因子与肿瘤的研究现状

恶性肿瘤的无限制侵袭性生长及其转移依赖于血管生成.因此,目前阻断血管形成探索抑制肿瘤的新途径之一.而血管内皮细胞生长因子(VEGF)是高度特异性的血管内皮细胞促分裂素,是重要的血管形成因子,从而支持肿瘤的生长.研究血管生成对了解恶性肿瘤发生、发展、侵袭、转移的生物学特性及针对肿瘤血管生成的基因治疗有重要的意义.     

血管内皮细胞生长因子及临床应用策略

血管内皮细胞生长因子 (VEGF)是一种特异作用于血管内皮细胞的多功能细胞因子 ,它能引起血管通透性增加 ,引起细胞外基质成分改变 ,诱导血管形成。在炎症、创伤愈合、心脏缺血、动脉粥样硬化、糖尿病性视网膜病变及肿瘤形成等与血管生成和病变有关的诸多病理过程中起重要作用。     

血管内皮细胞生长因子及其受体的分子生物学研究进展

血管内皮细胞生长因子(vascular endothelial cell growth factor,VEGF)是最直接的血管内皮细胞促分裂素,它通过其受体(VEGFR)介导其活性,不同VEGF剪接体与不同类型的VEGFR结合,通过胞内信号传导,发挥不同的生物学效应。本文总结了VEGF及其受体的结构、特点、分类、分子生物学特征、二者的连结及由VEGF诱导的胞内信号传导作用,并简单讨论了它们可能的应用前景。     

血管内皮生长因子的研究进展

本文介绍血管内皮生长因子的生物学特点从其受体在生理、缺血缺氧、肿瘤等方面的病理变化及意义。     

循证血管发生因子PD-ECGF、VEGF及抑制因子TSP-1在子宫内膜异位症发病因素中的作用

目的 :循证血小板衍化内皮细胞生长因子PD ECGF、血管内皮细胞生长因子VEGF、血小板反应素TSP 1在子宫内膜异位症 (EM )发病因素中的作用。方法 :3 0例需行手术治疗的EM患者 ,取其在位和异位内膜作免疫组化SP法检测PD ECGF、VEGF ,原位杂交法检测TSP 1的表达 ,以 3 0例非EM患者的子宫内膜作为对照 ,进行比较分析。结果 :异位内膜PD ECGF表达升高 ,EM患者子宫内膜TSP 1表达较对照组降低。结论 :PD ECGF参与了EM血管发生 ,EM患者子宫内膜抑制血管发生能力降低 ,使异位的内膜易于种植生长可能是EM发病的因素之一     

Vascular Endothelial Growth Factor (VEGF) in Autoimmune Diseases

Vascular endothelial growth factor (VEGF) is a potent stimulating factor for angiogenesis and vascular permeability. There are eight isoforms with different and sometimes overlapping functions. The mechanisms of action are under investigation with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins, which were not previously associated to angiogenesis. VEGF has important physiological actions on embryonic development, healing, and menstrual cycle. It also has a great role in pathological conditions that are associated to autoimmune diseases. There is considerable evidence in various autoimmune diseases such as in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis of an interrelationship between the VEGF system and theses disorders. Serum levels of VEGF correlate with disease activity in a large number of autoimmune diseases and fall with the use of standard therapy. We raised the possible future therapeutic strategies in autoimmune diseases with the anti-VEGF or anti-VEGFR (receptor). So far, this therapy has been used in cancer and macular ocular degeneration in diabetes. This review outlines the evidence for VEGF participation in various autoimmune diseases and proposes lines for future research in this field.     

转化生长因子β1及血管内皮细胞因子在颈椎病椎体软骨终板中的表达变化

目的：研究TGF-β1、VEGF在终板软骨细胞中的表达，探讨椎间盘退变的发病机理。方法：应用免疫组化SP染色法检测TGF-β1、VEGF在15例颈椎病及13例正常椎体软骨终板中的表达，并对其阳性表达结果进行比较。结果：TGF-β1在正常终板软骨细胞表达的阳性细胞数为39．0％±1．96％，与颈椎病终板软骨细胞表达的阳性细胞数28．2％±2．18％相比，差异有统计学意义（P〈0．05）。VEGF在正常的终板软骨细胞表达的阳性细胞数为22．2％±2．13％，与颈椎病终板软骨细胞表达阳性细胞数14．3％±1．68％相比，差异有统计学意义（P〈0．05）。结论：TGF-β1和VEGF共同参与了椎间盘退变的形成和发展，在椎间盘退变的发病中可能起重要的作用。调节细胞因子（TGF-β1、VEGF）在终板软骨细胞中的表达，可能为椎间盘退变的治疗提供一种新的途径。     

血管内皮生长因子(VEGF)对培养内皮细胞VEGF受体表达的影响

目的 :为探讨VEGF对培养内皮细胞 (EC)VEGF受体表达的影响。方法 :将培养的人脐静脉内皮细胞 (HUVEC)随机分为 4组 :( 1)正常对照组 ;( 2 )低氧培养组 ;( 3)VEGF 10ng/ml组 ;( 4)低氧 +VEGF10ng/ml组。HUVEC低氧培养参照Kuwara等介绍的方法并加以改进。HUVECVEGF受体的检测采用免疫组织化学方法。结果 :采用简易低氧培养法 ,48h内培养液氧分压维持在 5 8mmHg ;与对照组相比 ,低氧培养组、VEGF组和低氧 +VEGF组HUVECVEGF受体Flk 1/KDR阳性细胞数增多 ,强度增加 ;但未检测到VEGF受体Flt 1表达。结论 :低氧可使HUVEC表面的VEGF受体Flk 1/KDR表达增加 ,VEGF同源上调其受体Flk 1/KDR ,低氧和VEGF在调节VEGF受体Flk 1/KDR方面有协调作用。     

Immunohistochemical Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor in Canine Cutaneous Fibrosarcomas

The expression of five markers associated with tumour angiogenesis, proliferation and apoptosis was studied in 24 canine cutaneous fibrosarcomas. Tumours were assigned histological grades and were immunohistochemically evaluated for the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2). Additionally, intra-tumour microvessel density (iMVD) was assessed by immunohistochemical labelling for expression of von Willebrand factor (vWf) and tumour proliferation index (PI) was measured following labelling of Ki-67 antigen. Finally, tumour apoptotic index (AI) was determined by application of the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP end-labelling method (TUNEL). VEGF and VEGFR-2 expression were detected in 22/24 (92%) and 24/24 (100%) of fibrosarcomas, respectively. There was correlation between VEGF and VEGFR-2 expression (r = 0.51) and between histological grade and PI (r = 0.82). A significant difference in PI between tumours of different histological grade was found (P < 0.05). The median PI in grade 2 and 3 tumours (30.6 and 54.7, respectively) was significantly higher than in grade 1 tumours (6.4). Therefore, only PI correlates significantly with the histological grade of canine cutaneous fibrosarcomas. The potential for autocrine activity for VEGF exists in canine cutaneous fibrosarcomas, as VEGF and VEGFR-2 expression was found in most tumours.     

血管内皮生长因子与甲状腺疾病研究进展

血管内皮生长因子(VEGF)的基本功能是促进血管生长。近年研究表明,VEGF通过影响病灶处血管或癌细胞自身的生成从而在多种甲状腺疾病中发挥着重要作用。但VEGF的功能以及在不同甲状腺疾病中的具体变化情况仍然需要进一步探索。本文对VEGF的分子生物学及生物学特性、在多种甲状腺疾病中的作用及其临床应用进行简要综述。     

Level of Vascular Endothelial Growth Factor Predicts Both Relapse and Nonrelapse Mortality after Allogeneic Hematopoietic Stem Cell Transplantation

Although the prognostic significance of vascular endothelial growth factor (VEGF) has been researched extensively in patients with hematologic malignancies undergoing chemotherapy, its role in allogeneic hematopoietic stem cell transplantation (HSCT) requires further investigation. The present study evaluated the associations between VEGF level and relapse rate and early complications after HSCT. VEGF levels were analyzed in 91 consecutive patients before the start of conditioning, on day 0, on the day of engraftment, and on the day of diagnosis of veno-occlusive disease (VOD). Compared with a normal level, an elevated high VEGF-A level before conditioning was associated with an increased 2-year relapse rate (55% versus 24%, P = .003; hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.49 to 7.08) and decreased event-free survival (20% versus 44%; P = .022; HR, 2.03; 95% CI, 1.11 to 3.72). No association was found between VEGF level and the incidence of acute GVHD (P > .05). In patients with VOD, VEGF-A level was elevated on day 0 and on the day of VOD diagnosis (P < .05). A low VEGF-A level on day 0 was associated with reduced nonrelapse mortality (14% versus 35%; P = .048; HR, 0.32; 95% CI, 0.10 to 0.99). Our results indicate that a high VEGF-A level before HSCT increases the risk of relapse, and a high level after conditioning is associated with increased risks of early complications and nonrelapse mortality.     

Vascular Endothelial Growth Factor Is Increased in Patients With Preeclampsia

PROBLEM: This study was conducted to determine whether altered levels of vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of preeclampsia. METHOD OF STUDY: Maternal plasma samples were collected from 19 patients with preeclampsia (group A) either before the onset of labor, or before induction of labor or medical intervention. Plasma samples were also obtained from 19 normotensive patients with uncomplicated pregnancies (group B), who were matched with the patients with preeclampsia for gestational age and parity. Samples were frozen at ?70°C until assayed for VEGF by a specific enzyme-linked immunoassay. RESULTS: The mean maternal age was similar in groups A and B. For both groups the VEGF was detectable in all plasma samples. However, the plasma concentrations of VEGF were significantly increased in the group A patients, compared with those in group B (median, 47ng/ml; range, 10.6–72 ng/ml versus median, 13.6 ng/ml; range, 0.66-20 ng/ml; P < 0.001). In group A, a positive correlation was noted between VEGF concentrations and the systolic and diastolic blood pressure (r = 0.56; P = 0.01 and r = 0.48; P = 0.037, respectively). CONCLUSIONS: Maternal plasma VEGF levels were elevated in the patients with preeclampsia and correlated with the severity of hypertension, suggesting a role for VEGF in the pathogenesis of preeclampsia.