Vasohibin-1与糖尿病肾病

Vasohibin-1 (VASH-1)是一种以负反馈机制调节血管生成的内皮源性分泌蛋白.它能够以负反馈作用机制抑制血管内皮生长因子的作用,参与多种抗血管生成作用.作为机体的自我防御因子,VASH-1能够维持血管内皮的完整性,从而起到抵御糖尿病微血管并发症的作用.近年研究表明,VASH-1对肾小球内皮细胞和系膜细胞具有缓解微血管损害、调节炎性反应、延缓肾间质纤维化等重要功能,对糖尿病肾病具有重要的保护作用,可能成为糖尿病肾病早期治疗的一个新靶点.     

肿瘤血管生成的研究进展

血管生成 (angiogenesis)是指在原有微血管 (毛细血管和小静脉 )的基础上通过“出芽”的方式形成的毛细血管[1] 。 2 0世纪 70年代初 ,Folkman首先提出“肿瘤生长和转移都依赖于新生血管的形成”的概念[2 ] ,并得到大量实验结果的证实[3,4 ] ,目前这一概念已经形成共识。本文综述肿瘤血管生成特点、调控及抗血管生成治疗肿瘤的进展。　　一、肿瘤内血管生成特点　　早期的研究表明 ,在胚胎发育过程中造血细胞和血管发生的最初步骤开始于胚外卵黄囊的血岛形成。在受精卵发育第 7天时 ,中胚层细胞聚集并形成卵黄囊 ,其后 12小时中心部分的细…     

肿瘤血管生成及其抗血管生成治疗的研究进展

肿瘤的生长和转移依赖于新生血管形成,血管内皮生长因子及其受体是目前发现的最重要的促肿瘤血管生长因子,在肿瘤血管生成过程中发挥关键作用。鉴于肿瘤血管生成在肿瘤生长、浸润和转移中的重要作用,近年来开始了抗血管生成治疗肿瘤的新方法——抗血管生成疗法。本文着重综述了肿瘤血管生成及其抗肿瘤血管生成治疗的研究进展。     

胃癌血管生成研究进展

胃癌血管生成是胃癌发生、转移的基础。胃癌血管生成的机制十分复杂 ,促进胃癌血管生成因子较多 ,可概括为 4大类 :多肽细胞因子类、蛋白酶类、细胞粘附分子类和癌基因类。该文就近年来关于胃癌血管生成促进因子的研究作一综述。     

血管生成调控因子与肿瘤生长及治疗的研究进展

1968年Tannock IF发现肿瘤细胞分裂速率的减慢与营养血管的距离增大相关,肿瘤的氧气和营养供应限制了肿瘤生长.20世纪70年代,美国学者Folkman提出了肿瘤生长是依赖血管的.     

小肠腺瘤和腺癌促血管生长因子与抑制血管生成因子表达及意义

目的：研究小肠腺瘤和腺癌组织中碱性成纤维细胞（bFGF)，血小板衍生生长因子（PDGF）和血小板反应蛋白－1（TSP－1）三种mRNA表达水平及其临床病理意义。方法：收集小肠腺癌手术标本44例，病理类型包括腺癌Ⅰ、Ⅱ、Ⅲ级各11，26，7例；癌细胞未侵犯肌层或仅达浅肌层12例，侵犯深肌层18例，浆膜层14例。10例良性病变包括十二指肠腺瘤9例和回肠腺瘤1例。三种mRNA染色方法均为原位杂交染色法。结果：44例小肠腺瘤bFGF mRNA,PDGF mRNA和TSP－1 mRNA阳性率分别为57％，48％和36％，10例小肠腺瘤则分别为20％，30％和90％。小肠腺瘤bFGF mRNA阳性率明显高于腺瘤（P＜0．05），而SP－1 mRNA则相反（P＜0．05）。腺癌Ⅰ级＋Ⅱ级，癌细胞未侵犯肌层＋侵犯浅肌层，肿块最大径＜3cm和未见淋巴结转移病例，bFGF,mRNA,PDGF mRNA阳性率明显低于腺癌Ⅲ级，癌细胞侵犯深肌层＋浆膜层，肿块最大径≥3cm和淋巴结转移病例，但TSP－1mRNA表达则相反。bFGF mRNA在腺癌中表达与PDGF mRNA表达呈正相关，但与TSP－1mRNA表达呈负相关。结论：bFGF,PDGF和TSP－1均为重要的肿瘤血管生成调节因子，其中bFGF,PDGF mRNA表达与小肠癌发生，发展，生物学行为，转移及其预后有密切关系，为重要生物学标记物，而TSP－1mRNA表达者可能分化好，侵袭力弱，预后较好。     

肿瘤血管生成拟态的研究进展

恶性肿瘤的生长和转移必须以匹配合适的血液供应为前提，而阻断肿瘤的血液供应是攻克肿瘤治疗的一大策略，因此，肿瘤治疗的微循环机制及其结构与功能等，一直是国内外学者们研究的热点。以往的研究认为肿瘤血管是宿主正常的血管系统在肿瘤血管生成因子（Tumor angiogenesis factor，TAF）作用下，血管在形态和功能上发生了一系列改变而形成的。     

血管生成抑制蛋白Vasohibin的研究进展

对血管新生的促进在缺血性疾病包括动脉粥样硬化的干预具有实际意义,血管新生的调节依赖于促进因子和抑制因子的作用。Vasohibin是新近发现的调节血管生成的内皮源性负反馈调节因子,对抑制血管生成起重要作用。血管新生(angiogenesis)是指从已有的血管长出新血管的过程,生理和病理状态均可有新生血管形成。前者如正常胚胎发育、生殖、伤口愈合;而后者则可见于肿瘤、增殖性视网膜疾病、类风湿性关节炎等。血管新生的调节出现异常,则会导致病     

新的血管生成抑制肽(手性制剂)抗肿瘤血管生成的实验研究

目的 观察一种新的血管生成抑制胜对肿瘤的抑制作用，并探讨其作用机制。方法 体外药效实验，采用MTT法及血管内皮细胞迁移法，体内用Lewis肺癌瘤株皮下接种C57BL／6N小鼠，观察皮下移植瘤生长情况。结果 新的血管生成抑制胜对血管内皮细胞增殖、迁移有明显的抑制作用，在体内使Lewis肺癌皮下移植田体积明显缩小，毛细血管稀少。结论 新的血管生成抑制肽能明显抑制Lewis的肿瘤生长，其机制可能与抑制肿瘤血管生成有关。     

反应停抑制血管生成治疗血液肿瘤的研究进展

血管生成在实体瘤的发生、发展中的重要作用已被证实 ,且抗血管生成治疗实体瘤也取得了令人满意的效果。近年来 ,血液肿瘤的发生发展与血管生成的关系逐渐受到人们的关注。许多实验研究和临床观察的资料表明各种类型的白血病、淋巴瘤、多发性骨髓瘤等骨髓组织血管数目增加〔1〕、血清血管内皮生长因子 (ＶＥＧＦ)的水平增高 ,而且与疾病的发生和预后有关。反应停 (ｔｈａｌｉｄｏｍｉｄｅ)曾因严重的致畸作用而被禁用 ,近年来发现其具有抗血管生成作用 ,有望成为治疗血液肿瘤的有效药物。本文就这方面的研究进展作一综述。1 　 血管生成与血…     

肿瘤血管生成的实验研究方法

血管生成在肿瘤的生长与转移中具有重要的意义。各种促血管生成因子与血管生成抑制因子之间的平衡与失衡是肿瘤血管生成重要的调控因素。血管生成的实验研究模型各自有其优缺点,根据研究内容来选择合适的研究方法非常重要。离体模型简便易行,容易定量研究,可用于初步研究,但需在体模型的研究来进一步证实。在体模型操作繁琐、耗时,但更接近体内复杂的血管生成过程。     

Inhibitory effect of arsenic trioxide on angiogenesis and expression of vascular endothelial growth factor in gastric cancer

INTRODUCTION Arsenic has been used since ancient times as a therapeutic agent. However, until recently its use in modern medicine has been restricted to the treatment of a limited number of parastic infections. Since the early 1990s, arsenic trioxide (As2…     

Recent advances in endometrial angiogenesis research

This review summarises recent research into the mechanisms and regulation of endometrial angiogenesis. Understanding of when and by what mechanisms angiogenesis occurs during the menstrual cycle is limited, as is knowledge of how it is regulated. Significant endometrial endothelial cell proliferation occurs at all stages of the menstrual cycle in humans, unlike most animal models where a more precise spatial relationship exists between endothelial cell proliferation and circulating levels of oestrogen and progesterone. Recent stereological data has identified vessel elongation as a major endometrial angiogenic mechanism in the mid-late proliferative phase of the cycle. In contrast, the mechanisms that contribute to post-menstrual repair and secretory phase remodelling have not yet been determined. Both oestrogen and progesterone/progestins appear to have paradoxical actions, with recent studies showing that under different circumstances both can promote as well as inhibit endometrial angiogenesis. The relative contribution of direct versus indirect effects of these hormones on the vasculature may help to explain their pro- or anti-angiogenic activities. Recent work has also identified the hormone relaxin as a player in the regulation of endometrial angiogenesis. While vascular endothelial growth factor (VEGF) is fundamental to endometrial angiogenesis, details of how and when different endometrial cell types produce VEGF, and how production and activity is controlled by oestrogen and progesterone, remains to be elucidated. Evidence is emerging that the different splice variants of VEGF play a major role in regulating endometrial angiogenesis at a local level. Intravascular neutrophils containing VEGF have been identified as having a role in stimulating endometrial angiogenesis, although other currently unidentified mechanisms must also exist. Future studies to clarify how endometrial angiogenesis is regulated in the human, as well as in relevant animal models, will be important for a better understanding of diseases such as breakthrough bleeding, menorrhagia, endometriosis and endometrial cancer. Correspondence to: Dr Jane Girling, Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC 3168, Australia. Tel: +61-3-9594-5392; +61-3-9594-6389; E-mail: jane.girling@med.monash.edu.au     

MSCs transfected with hepatocyte growth factor or vascular endothelial growth factor improve cardiac function in the infarcted porcine heart by increasing angiogenesis and reducing fibrosis

Background

Cell transplantation and gene therapy have been demonstrated to have beneficial effects after a myocardial infarction (MI). Here, we used a large animal model of MI to investigate the beneficial effects of mesenchymal stem cells (MSCs) transfected with hepatocyte growth factor (HGF) or vascular endothelial growth factor (VEGF) genes.

Methods

A porcine MI model was created by balloon occlusion of the distal left anterior descending artery for 90 min followed by reperfusion. At 1 week after MI, the pigs were infused via the coronary vein with saline (n = 8), MSCs + AdNull(n = 8), MSC + VEGF(n = 10), or MSC + HGF(n = 10). Cardiac function and myocardial perfusion were evaluated by using echocardiography and gated cardiac perfusion imaging before and 4 weeks after transplantation. Morphometric and histological analyses were performed.

Results

All cell-implanted groups had better cardiac function than the saline control group. There were further functional improvements in the MSC + HGF group, accompanied by smaller infarct sizes, increased cell survival, and less collagen deposition. Blood vessel densities in the damaged area and cardiac perfusion were significantly greater in the MSC + AdNull group than in the saline control group, and further increased in the MSC + VEGF/HGF groups. Tissue fibrosis was significantly less extensive in the MSC and MSC + VEGF groups than in the saline control group and was most reduced in the MSC + HGF group.

Conclusion

MSCs (alone or transfected with VEGF/HGF) delivered into the infarcted porcine heart via the coronary vein improved cardiac function and perfusion, probably by increasing angiogenesis and reducing fibrosis. MSC + HGF was superior to MSC + VEGF, possibly owing to its enhanced antifibrotic effect.     

神经导向因子Netrin-1促进骨髓间充质干细胞的血管生成作用

将携带增强型绿色荧光蛋白(EGFP)基因标记的Netrin-1基因重组腺病毒(Ad5-EGFP-Netrin-1)或空载体的腺病毒(Ad5-EGFP)转染到大鼠骨髓间充质干细胞后与Matrigel胶混匀共同移植到大鼠皮下,分别在移植后14d和28d观察Netrin-1和血管内皮细胞生长因子(VEGF)的蛋白表达以及微血管形成数量的情况.结果显示,Netrin-1能促进VEGF的表达和血管形成,移植的细胞数量越多而作用越强(均P＜0.05)     

血管内皮细胞生长因子与治疗性血管新生

本文概述了血管内皮细胞生长因子(VEGF)家族及其受体的组成,介绍了调控VEGF表达的因素及VEGF信号传导途径。着重阐述了VEGF促血管新生的作用机制,以及VEGF在治疗性血管新生中的研究与应用现状、存在问题及未来发展前景。还简要介绍了VEGF其他的生物学作用。