血管生成抑制剂药物筛选模型的研究进展

在新药的研发中,药物筛选是必不可少的一个重要的环节,而如何建立有效的评价标准和实验模型是这一过程的关键。近年来,国际上一些体内外血管生成模型相继从分子、细胞、组织器官和整体水平上建立。     

抗血管生成药物筛选及其新模型——斑马鱼

目前抗血管生成疗法成为抗肿瘤研究的热点之一,抗血管生成药物筛选也已成为发现新型抗肿瘤药物的重要手段。筛选模型在药物筛选过程中起着关键性作用。本文评述了筛选抗血管生成类药物常用的分子、细胞、组织器官和整体动物等水平的筛选模型,并介绍了新的活体动物模型——模式生物斑马鱼。     

肿瘤血管生成抑制剂临床应用进展

血管生成抑制剂已被证明是一类有效的肿瘤治疗药物.概述了从单靶点、多靶点,到广谱血管生成抑制剂在临床上的应用;介绍了单克隆抗体、小分子和内源性的血管生成抑制剂及其相应靶点,讨论了新的靶点及有前景的新型血管生成抑制剂,希望为未来临床治疗提供切实的帮助.     

血管内皮细胞生长因子在损伤修复中的作用

近年研究显示血管内皮细胞生长因子能够促进局部组织的血管化,而血管生成是生理及病理性组织生长和损伤愈合的基础,故血管内皮细胞生长因子在损伤修复中有重要的作用。目前认为这一作用主要是促进内皮细胞有丝分裂和使细胞通透性增强,通过和血管内皮细胞的特异性受体结合,产生强大的促进内皮增殖及血管生成作用而实现的。     

血管内皮细胞分化实验模型的建立

取X期的鸡胚盘细胞进行体外培养,细胞于24h后开始贴壁生长,72h后,开始向上皮类细胞分化．用不同浓度的成纤维细胞生长因子（FGF）处理刚分离的胚盘细胞,结合间接免疫荧光法检测细胞第Ⅷ凝血因子相关抗原的表达,初步发现大于100μg/L的FGF能诱导胚盘细胞向内皮细胞分化．     

鼻咽癌细胞凋亡与血管生成的关系

摘要：为了探讨鼻咽癌（NPC）细胞凋亡及瘤内血管生成与患者预后的关系,采用TdT酶介导的生物素化dUTP缺口末端标记技术（TUNEL）和免疫组化S-P法,分别检测20例正常鼻咽粘膜组织及73例NPC组织的细胞凋亡率（Apoptosis Rate AR）、瘤内微血管密度（MVD）及血管内皮细胞生长因子（VEGF）的表达。其中,NPC复发转移组24例,未复发组49例。结果表明,正常鼻咽粘膜AR显著高于NPC（P〈0．01）,NPC复发转移组的MVD及VEGF显著高于未复发组（P〈0．05）,而AR则显著低于未复发组（P〈0．05）,MVD与VEGF、MVD与AR呈正相关（P〈0.05）。在NPC发展过程中,细胞凋亡明显受到抑制,VEGF是血管生成的重要因子,并通过促进血管生成影响患者的预后,说明细胞凋亡与NPC患者的预后有关系。     

血管内皮细胞生长因子在损伤修复中的作用

近年研究显示血管内皮细胞生长因子能够促进局部组织的血管化,而血管生成是生理及病理性组织生长和损伤愈合的基础,故血管内皮细胞生长因子在损伤修复中有重要的作用.目前认为这一作用主要是促进内皮细胞有丝分裂和使细胞通透性增强,通过和血管内皮细胞的特异性受体结合,产生强大的促进内皮增殖及血管生成作用而实现的.     

中药对肿瘤组织血管生成的影响

恶性肿瘤的无限制侵袭性生长及其转移依赖于血管生成（angiogenesis)抑制血管生成是不同于常规的肿瘤治疗新策略，肿瘤血管生成的过程是个多步骤过程，目前已进入临床的肿瘤血管生成抑制剂有数十种，许多有抗肿瘤活性的中药的有效成分，如：人参皂苷Rg^3、鲨鱼软骨生成抑因子（SCAIF）等可抑制肿瘤血管生成。     

天然产物抗血管生成的研究进展

抗血管生成治疗已成为恶性肿瘤治疗的重要途径。本文对近年来抗肿瘤血管生成的天然产物研究进行了归类,已有研究发现萜类、酚类、黄酮类、生物碱类和蒽醌类等天然产物有抑制血管生成的作用,并且通过细胞与分子学实验揭示了其抑制血管生成的机理。本文综述了近年天然产物抑制肿瘤血管生成的研究成果,希望能为中药材抗肿瘤药物开发提供新思路。     

血管内皮生长因子对缺血性脑血管病血管生成的作用研究

血管内皮生长因子是血管特异性生长因子,有促进内皮细胞增生、转移,增加血管通透性和促进血管生成的作用.阐述了血管内皮生长因子的生物学特性和功能,以及血管内皮生长因子与缺血性脑血管病的关系.     

冰箱回热毛细管计算模型

在分析现有的冰箱毛细管主要计算模型的基础上,针对冰箱毛细管实际应用情况,建立了冰箱回热毛细管六段流阻模型.该模型充分考虑了回气管与毛细管回热长度以及毛细管进出口截面突变的影响,并对冰箱回热毛细管在三种不同工况下的性能进行了模拟,研究了冷凝温度、蒸发温度、以及毛细管相对位置对毛细管工作性能的影响,结果显示冷凝温度对回热毛细管内的制冷剂流动特性影响最大.     

HERG1 K+ channels on the leukemic cells mediated angiogenesis in vitro

Human ether-a-go-go-related gene （HERG1） K^＋ channels are overexpressed in leukemia, which contributes to neoangiogene- sis. The purpose of this study was to investigate the role of HERG1 K^＋ channels on leukemia angiogenesis. We cultured human umbili- cal vein endothelial cells （HUVECs） in conditioned media, which were derived from leukemic cells with or without E-4031, a HERG1 K^＋ channel special inhibitor. The HUVECs proliferation was mea- sured using CCK-8 assay and migration by a Trans-well. Endothelial tube formation was investigated using Matrigel. Vascular endothelial growth factor （VEGF） levels were tested by ELISA and VEGF mRNA expression using RT-PCR. Our results revealed that blocking HERG1 K^＋ channels could inhibit leukemia-induced HUVECs pro- liferation, migration, and tube formation in vitro. The results sug- gested that HERG1 K~ channels could increase leukemia angio- genesis. Furthermore, blockage of HERG1 K^＋ channels could also decrease leukemic cells secreting VEGF and expressing VEGF mRNA. HERG1 K^＋ channels have a promoting effect on leukemia angiogenesis, and the possible mechanism may be that HERG1 K^＋ channels enhance VEGF expression. Thus, HERG1 K4 channel is a potential target of antiangiogenesis in leukemia.     

血管生成抑制剂与肺癌治疗的研究进展

目的:探讨血管生成抑制剂治疗肺癌的研究进展.方法:收集该类药物的国内外近期资料加以综合归纳.结果:血管生成抑制剂治疗肺癌方法可行,前景诱人.结论:随着血管生成抑制剂的不断开发和研究,对于肺癌这一血管增生明显的肿瘤,深入研究抗血管治疗具有重要意义.     

缠绕管换热器并管传热模型及实验

为了研究缠绕管式换热器中的并管结构的传热规律 ,对并管金属管壁的微元段建立热平衡方程 ,以管壁温度对称分布及通过两并管焊接结构的热量相等为边界条件 ,提出了并管传热模型。在以空气为工质的并管传热实验台上 ,测定了管壁温度 ,然后与模型计算管壁温度比较 ,验证了该传热模型的有效性。该模型是多流体并管式缠绕管换热器设计计算的基础。在低温和深冷分离工程中 ,这种结构紧凑可实现多流体换热的缠绕管式换热器 ,有着广泛的应用     

A novel <Emphasis Type="Italic">in vitro</Emphasis> angiogenesis model based on a microfluidic device

Angiogenesis is very important for many physiological and pathological processes. However, the molecular mechanisms of angiogenesis are unclear. To elucidate the molecular mechanisms of angiogenesis and to develop treatments for "angiogenesis-dependent" diseases, it is essential to establish a suitable in vitro angiogenesis model. In this study, we created a novel in vitro angiogenesis model based on a microfluidic device. Our model provides an in vivo-like microenvironment for endothelial cells (ECs) cultures and monitors the response of ECs to changes in their microenvironment in real time. To evaluate the potential of this microfluidic device for researching angiogenesis, the effects of pro-angiogenic factors on ECs proliferation, migration and tube-like structure formation were investigated. Our results showed the proliferation rate of ECs in 3D matrix was significantly promoted by the pro-angiogenic factors (with an increase of 59.12%). With the stimulation of pro-angiogenic factors gradients, ECs directionally migrated into the Matrigel from low concentrations to high concentrations and consequently formed multi-cell chords and tube-like structures. These results suggest that the device can provide a suitable platform for elucidating the mechanisms of angiogenesis and for screening pro-angiogenic or anti-angiogenic drugs for "angiogenesis-dependent" diseases.     

Effect of simvastatin on the atherosclerotic plaque stability and the angiogenesis in the atherosclerotic plaque of rabbits

In this study, the effect of simvastatin on the atherosclerotic plaque stability and the angiogenesis in the atherosclerotic plaque of rabbits was observed. Thirty New Zealand rabbits were randomly divided into the normal control group, the model control group and the simvastatin group, 10 in each group. Rabbits in the normal control group were fed with normal forage, while rabbits in the rest two groups were fed with high fat forage. The balloon injury was performed two weeks later to establish an abdominal aortic atherosclerosis model, and then high fat forage was successively fed to them. Meanwhile, simvastatin at the daily dose of 2.5 mg/kg body weight was administered to rabbits in the simvastatin group. After 6 weeks of successive administration, levels of blood lipids were measured after blood sampling, and the serum high sensitivity C-reactive protein （hsCRP） and matrix metalloproteinase-3,-9 （MMP-3,-9） were detected using enzyme-linked immunosorbent assay. The macroscopically pathological indices of the plaque tissue were observed using hematoxylin and eosin （HE） staining of abdominal aorta specimens under a light microscope, and the plaque area （PA）, cross-sectional vascular area （CVA） and correcting plaque area （PA/CVA） were determined quantitatively using imaging software. The protein expressions of the vascular endothelial growth factor （VEGF）, factor VIII related antigen （FVIIIRAg）, MMP-3 and cluster of differentiation antigen 40 ligand （CD40L） in the plaque were detected with the immunohistochemical method. Compared with the model control group, the levels of VEGF, FVIIIRAg, MMP-3, CD40L protein expression and the serum expression levels of hsCRP, MMP-3, MMP-9 in the simvastatin group were significantly reduced （P〈0.05, P〈0.01）. The ratio PA/CVA in the simvastatin group was more significantly reduced when compared with that in the model control group （P〈0.01）. The levels of serum total cholesterol （TC）, triglyceride （TG） and low-density lipoprotein cholesterol （LDL） were significantly reduced in the simvastatin group when compared with those in the model control group （P〈0.05, P〈0.01）. Simvastatin plays a certain role in stabilizing the atherosclerotic plaque, and inhibiting the angiogenesis in the atherosclerotic plaque may be one of possible mechanisms.     

Molecular imaging of tumor angiogenesis using RGD-labeled iron oxide nanoparticles

Integrin is often significantly up­regulated in activated endothelial cells during tumor angiogenesis. The arginine-glycine-aspartic acid (RGD) peptide sequence is a specific recognition motif to α_νβ₃ integrin. In this study, a RGD labeled, Poly lactic acid (PLA) coated ultrasmall paramagnetic iron oxide (USPIO) (referred to as RGD-PLA-USPIO) were developed and the ability to detect tumor angiogenesis was investigated in vitro and in vivo. Increased uptake of RGD-PLA-USPIO by human umbilical vein endothelial cells (HUVECs) was detected by Prussian blue stain and transmission electronic microscopy (TEM). Pronounced signal decrease in T₂^*-weighted magnetic resonance image (MRI) and heterogeneous arrangement of neovasculature of tumor tissue were clearly identified in Vx-2 tumor model. The MR signal of contralateral muscle only could be seen a slight background change after either RGD-PLA-USPIO or PLA-USPIO injection. These studies demonstrate the efficiency of RGD-PLA-USPIO to visualize α_νβ₃ integrin in activated tumor endothelial cells and its potential for detecting and monitoring tumor vasculature change after therapy.     

血管生成抑制素对体外培养的血管内皮细胞增殖与凋亡的影响

为研究血管生成抑制素对体外培养的血管内皮细胞生长的影响,采用MTT法观察细胞的增殖情况,利用Hoest染色和流式细胞仪检测细胞凋亡。结果发现血管生成抑制素能够抑制血管内皮细胞的增殖,其IC50为1.19 mg/L,并干扰内皮细胞的周期,出现G0/G1期阻滞。