雾化吸入碱性成纤维细胞生长因子对血管性痴呆患者血管内皮生长因子的影响

目的:研究雾化吸入碱性成纤维细胞生长因子(b-FGF)对血管性痴呆患者血清血管内皮生长因子(VEGF)的影响。方法:采用临床痴呆评定量表(CDR)筛选出轻度血管性痴呆(VD)患者60例,分成轻度VD治疗组34例,轻度VD对照组26例,另设正常对照组30例,VD对照组患者常规抗动脉硬化、抗血小板聚集及抗痴呆治疗,VD治疗组在其对照组常规治疗基础上给予b FGF 4800 AU/d加入生理盐水10 m L氧气雾化吸入,每次10 min,1次/d,连续14 d。比较2组VD患者治疗前、治疗后14、30 d血清VEGF的表达。结果:2组VD患者治疗前血清VEGF水平明显低于正常对照组,VD治疗组患者治疗后14、30 d血清VEGF水平逐渐升高,与VD对照组比较有统计学意义(P0.01)。结论:b FGF通过鼻黏膜进入中枢神经系统,促进VD患者血清VEGF的表达。     

碱性成纤维细胞生长因子对血管性痴呆大鼠海马区脑血管生成的影响

目的皮下注射碱性成纤维细胞生长因子于血管性痴呆大鼠,研究用药前后对大鼠海马区脑血管生成的影响。方法制作血管性痴呆大鼠模型,随机取用血管性痴呆大鼠模型12只,分碱性成纤维细胞生长因子处理组6只,生理盐水对照组6只。另外,取假手术组6只。皮下注射碱性成纤维细胞生长因子于血管性痴呆大鼠。治疗5周后,以Morris水迷宫定位航行试验和空间探索试验来检测大鼠的学习记忆能力,检测大鼠血清血管内皮生长因子变化,第Ⅷ因子相关抗原多克隆抗体免疫组织化学染色,观察海马阳性细胞数的变化。结果碱性成纤维细胞生长因子治疗5周后,假手术组、生理盐水对照组、碱性成纤维细胞生长因子处理组的平台象限滞留时间分别为14.3±3.1 s、7.4±2.9 s和12.6±2.7 s。假手术组和碱性成纤维细胞生长因子处理组的平台期保持时间要明显长于生理盐水对照组(P<0.05),显示碱性成纤维细胞生长因子处理组空间记忆能力较生理盐水对照组明显提高。假手术组、生理盐水对照组、碱性成纤维细胞生长因子处理组的血管内皮生长因子含量分别是8.14±1.53、6.07±0.18、9.19±0.29,碱性成纤维细胞生长因子处理组与生理盐水对照组比较有统计学意义(P<...     

辛伐他汀对高脂血症患者内皮功能障碍的干预作用及其与碱性成纤维细胞生长因子的关系

目的 研究辛伐他汀对高脂血症患者血管内皮功能障碍的干预作用及其与血清碱性成纤维细胞生长因子的关系.方法 将54例高脂血症患者按血脂水平随机分为辛伐他汀组(28例,辛伐他汀20 mg/d,8周)和高.脂对照组(26例),另设正常对照组(29例,正常健康受试者).应用彩色多谱勒超声诊断仪测量受试者肱动脉血流介导的舒张功能,评价血管内皮功能的变化.应用酶联免疫吸附双抗体夹心法和硝酸酶还原法检测受试者血清碱性成纤维细胞生长因子和一氧化氮的含量,评价一氧化氮及碱性成纤维细胞生长因子与血管内皮功能障碍的关系.常规检测血清总胆固醇、甘油三酯、低密度脂蛋白及高密度脂蛋白的浓度.结果 8周后,辛伐他汀组与高脂对照组相比肱动脉血流介导的舒张功能明显改善(P<0.05),血清一氧化氮和血清碱性成纤维细胞生长因子含量升高(P<0.05),血清总胆固醇、甘油三酯和低密度脂蛋白浓度明显下降(P<0.01),而高密度脂蛋白浓度明显升高(P<0.01).结论 辛伐他汀可增加血清碱性成纤维细胞生长因子含量,提高一氧化氮含量,改善高脂血症患者血管内皮功能障碍,其作用机制与降低血清总胆固醇、甘油三酯和低密度脂蛋白的浓度有一定关系.     

重组牛碱性成纤维细胞生长因子辅助治疗口腔溃疡的效果及对患者炎症因子的影响

目的 探究重组牛碱性成纤维细胞生长因子辅助治疗口腔溃疡的效果及对患者炎症因子的实际效用.方法 选取2018年2月-2019年1月就诊于本院的口腔溃疡患者共60例,依据入院先后分为两组,各30例.对照组应用常规药物治疗,观察组于前者基础上行重组牛碱性成纤维细胞生长因子辅助治疗,比较两组治疗前后炎性因子水平变化情况.结果 治疗前两组炎性因子无差异(P>0.05),治疗后观察组优于对照组(P<0.05).结论 重组牛碱性成纤维细胞生长因子辅助治疗口腔溃疡具显著疗效,改善患者炎症水平,临床价值高.     

沙利度胺对老年急性髓系白血病患者血清碱性成纤维细胞生长因子、血管内皮生长因子水平的影响

目的探讨沙利度胺对老年急性髓系白血病(AML)患者血清内碱性成纤维细胞生长因子(b-FGF)、血管内皮生长因子(VEGF)水平的影响。方法 90例老年AML患者随机分为两组各45例。对照组采用去甲基化治疗,观察组在此基础上加用沙利度胺治疗。比较两组血清b-FGF、VEGF水平、临床疗效及不良反应。结果治疗前,两组血清bF GF、VEGF水平相比差异无统计学意义(P0. 05);治疗后,两组血清bF GF、VEGF水平均明显低于治疗前,且观察组明显低于对照组(P0. 05);观察组临床治疗总有效率(77. 78%)明显高于对照组(46. 67%,P0. 05);两组不良反应发生率无统计学差异(P0. 05)。结论沙利度胺在老年AML治疗中疗效确切,可通过抑制血清bF GF、VEGF表达发挥抗血管生成作用。     

严重冠心病患者血清碱性成纤维细胞生长因子与冠状动脉侧支循环的相关性

目的探讨冠状动脉严重狭窄患者血清碱性成纤维细胞生长因子浓度与冠状动脉侧支循环形成、冠状动脉粥样硬化程度的关系。方法根据冠状动脉造影结果连续入选80例冠状动脉严重狭窄患者,按照Rentrop分级方法对冠状动脉侧支循环进行分级:0级26例,1级22例,2级18例,3级14例,采用酶联免疫吸附法检测血清碱性成纤维细胞生长因子浓度,并应用Gensini积分系统评价冠状动脉粥样硬化病变程度。结果冠状动脉侧支循环0级组碱性成纤维细胞生长因子血清水平为20.75±6.89 ng/L,1级组为22.04±5.18 ng/L,2级组为27.32±6.14ng/L,3级组为32.27±12.04 ng/L,随着侧支循环分级的增加,碱性成纤维细胞生长因子血清水平也相应增高(P<0.05);Spearman相关分析发现,冠状动脉侧支循环分级与碱性成纤维细胞生长因子血清水平呈正相关(P<0.01)。结论在冠状动脉严重狭窄的冠心病患者中,冠状动脉侧支循环形成良好患者碱性成纤维细胞生长因子血清浓度高于冠状动脉侧支循环形成不良患者;碱性成纤维细胞生长因子血清浓度与冠状动脉侧支循环分级呈正相关。     

川芎嗪注射液治疗不稳定型心绞痛的疗效及对血管内皮生长因子浓度的影响

目的观察川芎嗪注射液治疗不稳定型心绞痛（UA）的临床疗效及对血管内皮生长因子（VEGF）浓度的影响。方法将120例UA患者按随机性分为治疗组60例和对照组60例。两组均给予抗血小板药、硝酸酯类药物、B受体阻滞剂等治疗。治疗组在常规治疗基础上静滴川芎嗪注射液80mg／d加生理盐水250ml。14d后比较两组治疗后心绞痛情况，VEGF、纤维蛋白原（FIB）和血脂变化。结果治疗组心绞痛症状明显减少，血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）和FIB显著低于对照组，VEGF明显高于对照组，两组均无不良反应。结论川芎嗪注射液能增加血管内皮生长因子的含量。治疗不稳定型心绞痛疗效肯定。     

碱性成纤维细胞生长因子在烟草烟雾诱导大鼠血管平滑肌细胞增殖中的作用

目的探讨烟草烟雾提取物对大鼠血管平滑肌细胞增殖的影响及碱性成纤维细胞生长因子在其中的作用。方法按不同浓度烟草烟雾提取物(0、2.5%、5%、10%和20%)分为对照组、低浓度、中等浓度、高浓度和过高浓度烟草烟雾提取物组刺激血管平滑肌细胞,采用MTT法观察细胞增殖变化,免疫细胞化学法测定碱性成纤维细胞生长因子和增殖细胞核抗原蛋白的表达,同时用逆转录-聚合酶链反应法检测碱性成纤维细胞生长因子mRNA表达。用筛选出的最适烟草烟雾提取物浓度处理大鼠血管平滑肌细胞不同时间(0、4、8、12 h和24 h)后,检测碱性成纤维细胞生长因子mRNA及碱性成纤维细胞生长因子和增殖细胞核抗原蛋白的变化。用碱性成纤维细胞生长因子抗体和最适浓度烟草烟雾提取物干预血管平滑肌细胞24 h后检测细胞增殖及碱性成纤维细胞生长因子和增殖细胞核抗原蛋白表达的变化。结果 (1)与对照组相比,低浓度烟草烟雾提取物组(P0.05)和中浓度组血管平滑肌细胞增加明显(P0.01),而高浓度组和过高浓度组与对照组比较差异无显著性(P0.05)。碱性成纤维细胞生长因子mRNA、蛋白和增殖细胞核抗原蛋白在对照组中有少量表达,低浓度烟草烟雾提取物组表达增加(P0.01),中浓度烟草烟雾提取物组达到高峰,高浓度和过高浓度烟草烟雾提取物组仍高于对照组(P0.01)。(2)对照组(不加烟草烟雾提取物组即0 h组)血管平滑肌细胞中有少量碱性成纤维细胞生长因子mRNA、蛋白和增殖细胞核抗原蛋白表达。低浓度烟草烟雾提取物刺激4 h后细胞内碱性成纤维细胞生长因子mRNA、蛋白和增殖细胞核抗原蛋白表达增加(P0.01),碱性成纤维细胞生长因子mRNA于8 h达高峰;碱性成纤维细胞生长因子和增殖细胞核抗原蛋白于12 h达高峰。(3)碱性成纤维细胞生长因子抗体可显著抑制5%烟草烟雾提取物诱导的血管平滑肌细胞增殖和碱性成纤维细胞生长因子、增殖细胞核抗原蛋白表达增加。结论低浓度和中浓度烟草烟雾提取物对大鼠血管平滑肌细胞的促增殖作用逐渐增加;高浓度和过高浓度组时促增殖作用反而减弱。烟草烟雾提取物可能是通过增加碱性成纤维细胞生长因子的表达促进大鼠血管平滑肌细胞的增殖。     

血管性痴呆病人血清胰岛素样生长因子-1和颈动脉内膜-中层厚度的相关性研究

目的探讨血管性痴呆病人血清胰岛素样生长因子-1(IGF-1)与颈动脉内膜-中层厚度(IMT)的相关性。方法纳入临床诊断为血管性痴呆的病人60例,应用简易智力状态量表(MMSE)评分分组,26~30分为正常组(n=20),20~25分为轻度受损组(n=20),20分为中-重度受损组(n=20)。测量3组病人双侧颈总动脉IMT,以及血清IGF-1、血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、血糖水平,并进行组间比较分析,同时分析血清IGF-1与颈动脉IMT相关性。结果轻度受损组、中-重度受损组病人血清IGF-1浓度明显低于正常组,TG、TC、LDL-C水平明显高于正常组(P0.05);中-重度受损组血清IGF-1浓度亦低于轻度受损组(P0.05);轻度、中-重度受损组血管性痴呆病人IMT与正常组比较明显增厚(P0.05);中-重度受损组IMT较轻度受损组亦明显增厚(P0.05)。血清IGF-1与IMT呈负相关(r=-0.431,P0.05)。结论血管性痴呆的程度随着颈动脉IMT的增厚而加重;血清IGF-1与IMT呈负相关,IGF-1可能是血管性痴呆可监测的生物学指标。     

丁苯酞注射液联合依达拉奉对老年急性脑梗死患者细胞因子、血管内皮功能和氧化应激的影响

目的探讨丁苯酞注射液联合依达拉奉对老年急性脑梗死患者细胞因子、血管内皮功能和氧化应激的影响。方法选取120例老年急性脑梗死患者,随机分为观察组与对照组各60例。观察组采用丁苯酞注射液联合依达拉奉注射液治疗,对照组采用依达拉奉注射液治疗。两组疗程均为14 d。比较两组治疗14 d总有效率;治疗前与治疗14 d细胞因子[肿瘤坏死因子(TNF)-α、白介素(IL)-6和IL-8]、血管内皮功能[一氧化氮(NO)和血管内皮生长因子(VEGF)]、氧化应激[丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)]和美国国立研究院脑卒中量表(NIHSS)评分。结果观察组治疗14 d总有效率显著高于对照组(χ^2=8.640,P<0.05)。观察组治疗14 d血清TNF-α、IL-6和IL-8水平显著低于对照组(t=7.459、9.320、13.993,P<0.05)。观察组治疗14 d血清NO水平显著高于对照组,而VEGF水平显著低于对照组(t=10.637、29.253,P<0.05)。观察组治疗14 d血清MDA水平显著低于对照组,而GSH-Px和SOD水平显著高于对照组(t=10.127、9.575、22.761,P<0.05)。观察组治疗14 d NIHSS评分显著低于对照组(t=13.540,P<0.05)。结论丁苯酞注射液联合依达拉奉注射液对老年急性脑梗死患者疗效明显,可减轻患者炎症反应,改善患者血管内皮功能和氧化应激水平。     

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.     

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.     

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。     

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.     

Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma

Angiogenesis is a crucial process in the progression of multiple myeloma (MM). Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are multifunctional cytokines that potently stimulate angiogenesis including tumour neovascularization. Serum levels of VEGF and HGF were measured in 52 patients with MM by enzyme-linked immunosorbent assay (ELISA). Serum levels of VEGF and HGF were elevated in MM patients compared with healthy controls (VEGF: mean 0.31 ng/ml and 0.08 ng/ml respectively, P < 0.01; HGF: mean 2.17 ng/ml and 0.45 ng/ml, respectively, P < 0.001). In serial samples taken after chemotherapy, serum VEGF and HGF levels were correlated with M-protein levels. Serum levels of VEGF were higher in patients with extramedullary plasmacytomas than in patients without them (P < 0.05). They were also significantly higher in a group of patients who showed poor response to chemotherapy (P < 0.01). Serum levels of HGF were higher in patients with complications such as anaemia, hypercalcaemia and amyloidosis than in patients without these complications (P < 0.01, P < 0.05, P < 0.05 respectively). Both serum VEGF and HGF levels were significant predictors of mortality (P = 0.01, P = 0.02, respectively, log-rank test). The present study demonstrated that serum levels of VEGF and HGF are significantly elevated and dependent on the severity of MM, suggesting that measurement of VEGF and HGF may be useful for assessing disease progression and for predicting the response to chemotherapy in MM patients.