白三烯受体拮抗剂对致敏大鼠血管内皮生长因子及其受体表达的影响

目的 研究白三烯受体拮抗剂(孟鲁司特)对支气管哮喘(简称哮喘)气道炎症和气道重塑的影响,揭示白三烯受体拮抗剂对血管内皮生长因子(VEGF)及其受体的调控作用.方法 将24只清洁级雄性SD大鼠按随机数字表法分为对照组、哮喘组和干预组,每组8只.对照组采用生理盐水致敏和激发,哮喘组采用卵清白蛋白致敏和激发,干预组在采用卵清白蛋白致敏和激发前给予孟鲁司特灌胃.采用肺功能检测各组大鼠气道呼气阻力;采用酶联免疫吸附法(ELISA)对各组大鼠血清中VEGF和白三烯D<4>(LTD4)进行定量分析;用免疫组织化学方法检测VEGF、VEGF受体1(VEGFR1)及VEGFR:在大鼠肺组织内的表达水平.采用图像分析软件测定肺组织切片中的血管计数、血管平滑肌厚度.结果 (1)肺功能检测显示哮喘组平均呼气阻力显著升高;(2)对照组血清中VEGF和LTD4的水平分别为(17±5)ng/L和(6.1±0.7)ng/L,哮喘组分别为(31±6)ng/L和(10.7±3.5)ng/L,干预组分别为(15±4)ng/L和(9.8±1.6)ng/L,对照组和干预组分别与哮喘组比较差异有统计学意义(F值分别为63.78和39.56,均P<0.01);(3)免疫组织化学结果显示哮喘组VEGF及受体均大量表达,而对照组和干预组有较少表达.(4)图像分析显示,对照组、哮喘组和干预组的血管计数分别为14±2、22±2和16±4.(5)直线相关分析显示,血管计数与血清中VEGF的水平正相关(r=0.705,P<0.05).结论 VEGF及其受体在哮喘气道及肺内过度表达,参与了气道炎症和气道血管重塑的过程.孟鲁司特可能通过影响VEGF及其受体的表达影响气道炎症和气道血管重塑的病理生理过程.     

血管内皮生长因子水平与大鼠支气管哮喘模型发病机制关系的研究

目的 探讨大鼠支气管哮喘(简称哮喘)模型支气管肺泡灌洗液(BALF)中血管内皮生长因子(VEGF)水平与哮喘嗜酸粒细胞(EOS)炎症及气道血管通透性之间的关系,以及吸入性激素的作用.方法 SD大鼠18只,随机分为对照组,哮喘模型组和地塞米松干预组各6只.以腹腔注射1%卵蛋白致敏和2%卵蛋白雾化吸入激发复制哮喘模型,干预组在每次激发前给予地塞米松干预.检测大鼠气道反应性,BALF中EOS百分数,VEGF(酶联免疫吸附法)及气道血管渗透指数.结果 BALF中EOS百分数,VEGF水平,气道反应性及气道血管渗透指数哮喘组明显高于对照组(P<0.05或P<0.01);经过6周吸入性激素治疗后,地塞米松组BALF中VEGF水平,EOS百分数,气道反应性及气道血管渗透指数较哮喘组明显降低(P<0.05或P<0.01),与对照组比较差异无统计学意义.相关分析显示,BALF中VEGF水平与EOS百分数呈正相关(r=0.76,P<0.01);VEGF水平与气道血管渗透指数呈正相关(r=0.84,P<0.01);VEGF水平与PC50呈负相关(r=-0.68,P<0.01).结论 大鼠哮喘模型BALF中VEGF水平增高,并与气道EOS百分数,气道反应性和气道血管渗透指数密切相关.该结果提示VEGF可能在哮喘的发病机制中起着重要作用.     

血管内皮生长因子水平与大鼠支气管哮喘模型发病机制关系的研究

目的 探讨大鼠支气管哮喘（简称哮喘）模型支气管肺泡灌洗液（BALF）中血管内皮生长因子（VEGF）水平与哮喘嗜酸粒细胞（EOS）炎症及气道血管通透性之间的关系,以及吸人性激素的作用.方法 SD大鼠18只,随机分为对照组,哮喘模型组和地塞米松干预组各6只.以腹腔注射1%卵蛋白致敏和2%卵蛋白雾化吸入激发复制哮喘模型,干预组在每次激发前给予地塞米松干预.检测大鼠气道反应性,BALF中EOS百分数,VEGF（酶联免疫吸附法）及气道血管渗透指数.结果 BALF中EOS百分数,VEGF水平,气道反应性及气道血管渗透指数哮喘组明显高于对照组（P〈0.05或P〈0.01）;经过6周吸人性激素治疗后,地塞米松组BALF中VEGF水平,EOS百分数,气道反应性及气道血管渗透指数较哮喘组明显降低（P〈0.05或P〈0.01）,与对照组比较差异无统计学意义.相关分析显示,BALF中VEGF水平与EOS百分数呈正相关（r=0.76,P〈0.01）;VEGF水平与气道血管渗透指数呈正相关（r=0.84,P〈0.01）;VEGF水平与PC50呈负相关（r=-0.68,P〈0.01）.结论 大鼠哮喘模型BALF中VEGF水平增高,并与气道EOS百分数,气道反应性和气道血管渗透指数密切相关.该结果提示VEGF可能在哮喘的发病机制中起着重要作用.     

吸入布地奈德/福莫特罗干粉剂治疗轻中度支气管哮喘急性发作的疗效观察

目的 评价布地奈德／福莫特罗干粉剂吸入治疗轻中度支气管哮喘急性发作的疗效。方法 96例轻中度支气管哮喘急性发作患者随机分为吸入布地奈德／福莫特罗组和口服强的松／吸入布地奈德组，在治疗前及治疗后第3、6天行肺功能检查，并观察患者的哮喘症状及体征变化。结果 吸入布地奈德／福莫特罗与口服强的松／吸入布地奈德均能明显改善轻中度支气管哮喘急性发作患者的肺功能和症状，但二者疗效相比无明显差异。结论：吸入布地奈德／福莫特罗可以替代口服强的松／吸入布地奈德而作为轻中度支气管哮喘急性发作的治疗用药。     

膀胱移行细胞癌VEGF和VEGFR的表达及相关性的探讨

目的　探讨膀胱移行细胞癌 (BTCC)中血管内皮生长因子 (VEGF)及其受体 (VEGFR)的表达及与两者之间的关系。方法　采用免疫组织化学链霉菌抗生物素 过氧化物酶连接法 (S P法 )对 30例BTCC及 1 0例正常膀胱黏膜组织中VEGF及VEGFR的表达进行检测。结果　VEGF和VEGFR在绝大多数BTCC中呈阳性表达 ,平均表达率分别为 87%和 73 %。随肿瘤分期和分级的升高其表达水平升高 ,但在正常膀胱组织中未见表达。结论　BTCC中VEGF和VEGFR表达阳性 ,提示其在BTCC的血管生成和侵袭进展过程中起着重要作用 ,并将有可能为BTCC抗血管形成治疗及预防提供新的思路     

小剂量布地奈德/福莫特罗干粉吸入联合茶碱缓释片口服治疗中度哮喘的疗效观察

目的 探讨小剂量布地奈德/福莫特罗干粉联合茶碱缓释片治疗中度支气管哮喘(简称哮喘)的疗效、安全性及药物经济学.方法 选择60例中度哮喘患者,随机均分为A、B两组.A组给予布地奈德/福莫特罗干粉吸入(80、4.5 μg/吸)早、晚各1次,茶碱缓释片0.2g/次、1次/12 h口服;B组给予布地奈德/福莫特罗干粉吸入(160、4.5μg/吸)早、晚各1次.疗程均为12周.观察治疗前后两组临床症状、肺功能、药物不良反应情况,并比较两组治疗费用.结果 两组治疗后临床基本控制率、哮喘控制测试评分、第1秒用力呼气容积(FEV1)和FEV1占预计值的百分比均优于治疗前(P均＜0.01),而两组治疗后比较差异无统计学意义(P均＞0.05).两组不良反应发生率比较差异无统计学意义(P＞0.05).A组3个月人均药物治疗费用较B组低(P＜0.05).结论 小剂量布地奈德/福莫特罗干粉联合茶碱缓释片治疗中度哮喘疗效较好,不良反应较轻,且治疗费用较低.     

HIF-1α、VEGF、VEGFR2在非小细胞肺癌组织中的表达及临床意义

目的探讨非小细胞肺癌（NSCLC）病理组织中乏氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）、血管内皮生长因子受体2（VEGFR2）的表达情况及临床意义。方法采用免疫组化方法测定50例非小细胞肺癌组织和10例肺良性病组织中HIF-1α、VEGF、VEGFR2表达情况,并结合患者的临床病理资料进行分析。结果 50例非小细胞肺癌组织中HIF-1α、VEGF、VEGFR2高表达率分别为58%、54%、60%。三者在非小细胞肺癌组织中均有高表达,与对照组比较差异有显著性（P〈0.01）。HIF-1α、VEGF、VEGFR2表达与肿瘤的TNM分期、淋巴结转移和肿瘤组织分化程度有关（P〈0.05）,而与患者年龄、性别、病理类型无关（P〉0.05）。HIF-1α的表达与VEGF、VEGFR2表达呈显著正相关（P〈0.01）。结论非小细胞肺癌中HIF-1α、VEGF、VEGFR2表达水平有相关性,它们在非小细胞肺癌发生、发展和转移中有重要意义,对临床判断非小细胞肺癌预后和指导临床抗血管生成有一定的价值。     

血管内皮生长因子受体信号转导通路与生物学效应

血管生成是指从已存在的血管中以出芽的方式生成新血管的过程。血管内皮细胞生长因子（VEGF）能促进生理和病理的血管生成。VEGF有两个主要的酪氨酸激酶受体：VEG—FR—1（Fit—1）和VEGFR—2（KDR／Flk—1）。VEGF的生物学效应主要是通过VEGFR—2实现的，多种信号蛋白的激活均与VEGF的信号转导有关，涉及促内皮细胞生存、增殖、迁移，促进血管渗透增加，促进NO合成及释放等多项生物学功能。     

VEGF和Livin在肾癌组织中的表达与临床分期的意义

目的检测不同临床时期肾癌患者癌组织血管内皮生长因子(VEGF)、血管内皮生长因子受体(VEGFR)和Livin表达,探讨VEGF、VEGFR和Livin在肾癌组织中的表达与临床分期的意义。方法蛋白质免疫印迹法、酶联免疫吸附法和RT-PCR检测癌组织Livin,蛋白质免疫印迹法和RT-PCR检测癌组织VEGF、VEGFR。结果肾癌组织中VEGF、VEGFR和Livin明显表达,随着病程的进展VEGF、VEGFR和Livin活性逐渐增高,以Ⅳ期最明显,Livin与VEGF、VEGFR表达具有正相关性。结论 VEGF、VEGFR和Livin可能参与肾癌临床病情进展,也参与肾癌的发病机制。     

布地奈德联用福莫特罗与双倍剂量布地奈德吸入治疗支气管哮喘的对照研究

目的　比较联合吸入布地奈德和福莫特罗与吸入双倍剂量布地奈德治疗轻、中度支气管哮喘的临床疗效和安全性。方法　采用开放随机平行对照的方法 ,将患者随机分成两组 :(1)观察组 :原有吸入布地奈德40 0～ 80 0 μg/d剂量不变 ,加上福莫特罗 9μg ,每日 2次 ;(2 )对照组 :双倍原有布地奈德剂量 ,即 80 0～ 16 0 0 μg/d。每组 30例 ,疗程 12周。结果　观察组患者平均晨晚间最大呼气流量 (PEF)值的改善和无症状天数的增加较对照组明显 ,两组间有统计学差异。药物不良反应发生率试验组与对照组分别为 3 2 %与 6 3% ,两组间无统计学差异。结论　布地奈德联用福莫特罗 ,通过两者协同互补效应 ,有效改善肺功能、病人生活质量和控制哮喘症状。     

血管内皮生长因子及其受体在肺气肿患者肺组织中的表达

目的探讨血管内皮生长因子(VEGF)及其受体2(VEGF受体2/KDR)在肺气肿患者肺组织中的表达及其与肺气肿的相关性。方法取35例行肺叶切除术患者[A组(吸烟伴肺气肿组)16例,B组(不吸烟肺功能正常组)14例,C组(吸烟但肺功能正常组)5例]的外周肺组织标本,ELISA法检测肺组织匀浆中VEGF的含量,免疫组化法检测KDR蛋白表达,RT PCR检测VEGF和KDRmRNA水平,TUNEL法检测肺泡隔细胞的凋亡。结果A组患者肺组织VEGF、KDR表达均低于B组(P<0.01),肺泡隔细胞凋亡率高于B组(P<0.01)。C组与B组相比,VEGF及KDR表达差异无统计学意义(P>0.05)。结论VEGF及KDR水平减少与肺泡隔细胞凋亡的增加可能与肺气肿的发生相关。     

Novel vascular endothelial growth factor binding domains of fibronectin enhance vascular endothelial growth factor biological activity

Interactions between integrins and growth factor receptors play a critical role in the development and healing of the vasculature. This study mapped two binding domains on fibronectin (FN) that modulate the activity of the angiogenic factor, vascular endothelial growth factor (VEGF). Using solid-phase assays and surface plasmon resonance analysis, we identified two novel VEGF binding domains within the N- and C-terminus of the FN molecule. Native FN bound to VEGF enhanced endothelial cell migration and mitogen-activated protein (MAP) kinase activity, but FN that is devoid of the VEGF binding domains failed to do so. Coprecipitation studies confirmed a direct physical association between VEGF receptor-2 (Flk-1) and the FN integrin, alpha5beta1, which required intact FN because FN fragments lacking the VEGF binding domains failed to support receptor association. Thrombin-activated platelets released intact VEGF/FN complexes, which stimulated endothelial cell migration and could be inhibited by soluble high affinity VEGF receptor 1 and antibodies to alpha5beta1 integrin. This study demonstrates that FN is potentially a physiological cofactor for VEGF and provides insights into mechanisms by which growth factor receptors and integrins cooperate to influence cellular behavior.     

血管内皮生长因子及血管内皮生长因子受体在急性肺损伤中作用的研究

血管内皮生长因子是作用于血管内皮细胞的重要血管调节因子,它通过与内皮上的特异受体结合,可发挥促进内皮细胞增殖、分化、诱导血管生成、增加微血管通透性等多种功能.近年研究显示血管内皮生长因子在不同原因、不同阶段急性肺损伤中所起的作用不同.     

Vascular endothelial growth factor and vascular homeostasis

Vascular endothelial growth factor (VEGF) is the angiogenic factor promoting and orchestrating most, if not all, processes of neovascularization taking place in the embryo and the adult. VEGF is also required to sustain newly formed vessels and plays additional multiple roles in the maintenance and function of certain mature vascular beds. Correspondingly, perturbations in VEGF signaling may impact organ homeostasis in multiple ways. Here we briefly review potential consequences of VEGF loss of function in adult organs. Different vascular beds display highly variable dependencies on VEGF for survival, and its loss of function may trigger the regression of many VEGF-dependent vasculatures. Normal turnover of blood vessels, in conjunction with the fact that VEGF is indispensable for compensatory angiogenesis to restore adequate perfusion, accounts for progressive vascular rarefaction under conditions of chronic VEGF inhibition of even vasculatures that are not intrinsically dependent on VEGF. Because blood vessels may have paracrine functions other than their traditional role in tissue perfusion, vascular regression resulting from VEGF withdrawal may cause substantial collateral tissue damage. VEGF may also impact tissue homeostasis via acting directly on nonvascular cells expressing cognate receptors. In the particular case of the lung, constitutive abundant expression of VEGF together with the fact that its receptors are distributed on both endothelial and epithelial cells is compatible with multiple homeostatic VEGF functions in the adult lung. Indeed, experimental inhibition of VEGF in the mature lung produces lesions resembling common lung pathologies, including emphysema and respiratory distress syndrome.     

Therapeutic angiogenesis using vascular endothelial growth factor

Therapeutic angiogenesis using vascular endothelial growth factor can reduce tissue ischemia by simulating the natural process of angiogenesis. Vascular endothelial growth factor not only stimulates endothelial cells to proliferate and migrate, but also mobilizes endothelial progenitor cells and achieves vascular protection. Besides direct administration of angiogenic proteins, plasmids and viral vectors carrying angiogenic genes have been used. Animal experiments have shown promise with evidence of neovascularization and improved perfusion in the target myocardium. Initial phase I and II clinical trials results are encouraging and reflect the potential success of therapeutic angiogenesis as a clinical modality for the treatment of ischemic heart disease. This review discusses the role of vascular endothelial growth factor in therapeutic angiogenesis, along with the problems and considerations of this approach as a treatment strategy.     

神经发生、血管内皮生长因子与血管性认知损害

神经发生是神经前体细胞自我增殖和分化产生新神经元的动态过程。研究证实,海马神经发生可改善认知功能,并且血管内皮生长因子(vascular endothelial growth factor, VEGF)在神经发生中发挥着重要的调控作用。文章就 VEGF 促进神经发生的机制以及神经发生改善血管性认知损害的作用进行了综述。     

Hepatocyte growth factor and vascular endothelial growth factor in ischaemic heart disease

BACKGROUND: Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors, but the production of these growth factors in cardiomyocytes has also been demonstrated. However, there have been no reports focusing their attention on the changes in these growth factors after coronary intervention. We investigated the time-course changes of the serum VEGF and HGF levels in angina pectoris (AP) and acute myocardial infarction (AMI). METHODS: The serum HGF and VEGF levels were measured in 60 patients with AP, in 62 patients with AMI (AP, before heparin administration, and at 24 and 48 hours, and one week after intervention; AMI, before heparin, and at 48 and 72 hours, and one, two, three and four weeks) and in 56 patients with neurocirculatory asthenia as controls. We defined the patients with remodelling who showed an increase in left ventricular end-diastolic volume index (LVEDVI) in the sub-acute phase of AMI. RESULTS: Hepatocyte growth factor levels in the AP and AMI were significantly higher than that in the control (p<0.0001). The AMI level was also significantly higher than AP (p<0.001). In the AMI and AP, HGF peaked at 48 hours. Vascular endothelial growth factor level in the AMI was significantly higher than that in the control and AP (p<0.0001). In the AMI, VEGF peaked at two weeks. There was a significant positive correlation between the peak VEGF and LVEDVI in the sub-acute phase of AMI (p=0.0089, r=0.436). Peak VEGF in the remodelling (+) group was significantly higher than that in the remodelling (-) group (p<0.001). In the AP, VEGF was unchanged. CONCLUSION: While both myocardial and vascular damage contribute to an increase in HGF level, vascular damage is not associated with the increase in VEGF. Vascular endothelial growth factor might be related to left ventricular remodelling in the sub-acute phase of myocardial infarction.     

Elevated vascular endothelial growth factor in systemic sclerosis

OBJECTIVE: To determine the serum levels of vascular endothelial growth factor (VEGF) in patients with systemic sclerosis (SSc) and to search for relationships between its serum levels and the clinical manifestations. METHODS: Serum levels of VEGF in patients with SSc and healthy controls were determined by ELISA. At the time of blood sampling, individual organ involvement was assessed, and a video microscope and PC based image processing were used to visualize nailfold capillaries and to quantify capillary density. RESULTS: Serum levels of VEGF in 48 patients with SSc were significantly higher than in 30 controls (432 +/- 356 vs 91 +/- 64 pg/ml; p < 0.001). Patients with diffuse cutaneous SSc (n = 21) had higher levels of serum VEGF than those with limited cutaneous SSc (n = 27) (432 +/- 356 vs 135 +/- 127 pg/ml; p < 0.001). Serum VEGF levels correlated well with the extent of skin sclerosis, as determined by modified Rodnan skin score (r = 0.656, p < 0.001) and serum TGF-beta levels (r = 0.530, p < 0.001). In particular, serum VEGF levels were inversely correlated with the capillary density of nailfold (r = -0.649, p < 0.001). However, no significant differences were found in the serum levels of VEGF between patients with systemic organ involvement and those without. CONCLUSION: The extent of skin sclerosis may contribute to the elevation of serum VEGF and high VEGF levels may serve as a surrogate indicator of capillary damage in SSc.     

VEGF对血管内皮细胞损伤的拮抗作用及作用机制

冻结性冷损伤是以组织冻结再融化过程的病理改变为基础的损伤。已经证实,血管内皮细胞（VECs）除有屏障和膜转运功能外,还具有内分泌功能,主动参与了多种生命活动,对维持体内环境的平衡与稳定具有重要作用。冻伤过程中VECs的损伤,可促进微循环血栓形成造成微循环障碍;待到复温后,血液恢复流动又可导致不可逆的再灌注损伤。因此,减轻内皮细胞损伤,可以减少微循环血栓形成,从而减轻再灌注对机体造成的损伤。血管内皮细胞生长因子（VEGF）作为重要的血管生长因子,在冻伤时对VECs损伤具有拮抗作用,可通过促进血管再生、抗血栓形成、抑制血管平滑肌过度生长及抗炎的作用等实现的对血管的保护作用,为临床防治冻伤提供了新的思路。