内皮祖细胞对小鼠肾癌血管新生化的影响

目的 检测内皮祖细胞（EPCs）在小鼠肾癌（RCC）中的分布特征,探讨EPCs在肾癌新生血管化中的作用。方法 雄性BALB／c裸鼠70只按数字表法随机分为A组（35只）、B组（35只）,另取6只作为对照组（C组）。A组小鼠右肾下极移植人肾癌细胞,B组为假手术,C组不做任何处理;于实验后21、28、35、42、49d,A、B、C组各时间点分别处死7只、7只和1只小鼠,收集标本评估C组右侧正常肾组织（NT）、B组右肾损伤肾组织（ST）、A组的癌组织（1Tr）和癌旁组织（AT）中EPCs水平及分布,以及微血管密度（MVD）、血管内皮生长因子（VEGF）、基质细胞衍生因子（SDF-1）、内皮生长因子受体2（FLK）、趋化因子受体（CXCR4）等mRNA表达。结果 流式细胞仪检测显示,AT中EPCs水平在28d后逐渐升高,明显高于TT、NT及ST中的表达（P〈0．05）;TT中EPCs水平则先升高以后逐渐降低,且明显高于NT中表达（P〈0．05）。免疫荧光检测EPCs主要聚集于AT;免疫组织化学检测AT中MVD明显高于TT和NT,而TT中MVD则低于NT（P〈0．05）;AT中VEGF、FLK、SDF-1和CXCR4 mRNA水平对比,TT和NT明显升高（P〈0．05）。结论 EPCs可通过分泌促血管内皮生长因子和参与血管形成来参与肿瘤新生血管化,并以此促进肾癌的进展。     

体外冲击波疗法对促进创面血管生成及愈合作用的研究进展

改善创面循环血量对创面的快速愈合具有重要意义.研究显示,体外冲击波疗法（extracorporeal shock wave therapy,ESWT）对创面血管生成及创面愈合具有促进作用.本文查阅关于ESWT对创面血管再生及促进创面愈合作用的实验及临床研究论文,并对检索结果进行整理、综合与分析.目前研究结果显示,ESWT照射可通过上调血管生成及组织再生因子,如血管内皮生长因子、内皮型一氧化氮合酶以及增值性细胞核抗原的表达,增加组织灌注,改善局部血液供应,促进组织再生.虽然ESWT可有效改善局部血液供应及促进组织再生,但ESWT应用时的能量、聚焦程度、频率及周期数的最佳设置还有待于进一步研究.     

Design of a composite biomaterial system for tissue engineering applications

Biomaterials that regulate vascularized tissue formation have the potential to contribute to new methods of tissue replacement and reconstruction. The goal of this study was to develop a porous, degradable tissue engineering scaffold that could deliver multiple growth factors and regulate vessel assembly within the porous structure of the material. Porous hydrogels of poly(ethylene glycol)-co-(l-lactic acid) (PEG–PLLA) were prepared via salt leaching. The degradation time of the hydrogels could be controlled between 1 and 7 weeks, based on hydrogel composition. Fibrin was incorporated into the interconnected pores of the hydrogels to promote neovascularization and as a reservoir for rapid (<5 days) growth factor delivery. Poly(lactic-co-glycolic acid) (PLGA) microspheres were incorporated into the degradable polymeric hydrogel scaffold to allow sustained (>30 days) growth factor delivery. Fibroblast growth factor-1 (FGF-1) and platelet-derived growth factor-BB (PDGF-BB) were delivered from the system owing to their roles in the promotion of angiogenesis and vascular stabilization, respectively. Hydrogels tested in vivo with a subcutaneous implantation model were selected based on the results from in vitro degradation and growth factor release kinetics. Dual growth factor delivery promoted significantly more tissue ingrowth in the scaffold compared with blank or single growth factor delivery. The sequential delivery of FGF-1 following PDGF-BB promoted more persistent and mature blood vessels. In conclusion, a biomaterials system was developed to provide structural support for tissue regeneration, as well as delivery of growth factors that stimulate neovascularization within the structure prior to complete degradation.     

血管内皮生长因子靶向抗肿瘤药物的研究与开发

血管内皮生长因子（VEGF）家族在肿瘤血管生成与转移中起关键作用,从不同途径阻断VEGF的生物学作用可以达到治疗肿瘤的目的。目前以VEGF及其受体为靶标研究开发了抗体、可溶性受体、酪氨酸激酶抑制剂、核酸和多肽类药物,均取得了较好的进展。     

2-甲氧雌二醇的抗乳腺癌作用及其机制

2-甲氧雌二醇（2-ME）是雌二醇的一种天然代谢产物,具有包括抗乳腺癌在内的广谱抗肿瘤作用。研究发现,这种抗肿瘤作用主要与其抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡及抑制血管生成有关,而与雌激素受体无关。因此被认为可以用于乳腺癌治疗。2-ME因可口服、不良反应轻、与其他抗癌药物有协同作用而无交叉耐药,具有良好的应用前景。     

三七皂苷对高氧诱导的早产儿视网膜病变小鼠血管新生及脂联素和肿瘤坏死因子-α表达的影响

目的 研究三七皂苷对高氧诱导的早产儿视网膜病变(ROP)小鼠血管新生及脂联素(APN)和肿瘤坏死因子-α(TNF-α)表达的影响.方法 将45只新生C57BL/6J小鼠按随机数字表法分为正常对照组、ROP组和三七皂苷组,每组15只.采用Smith法建立ROP模型.三七皂苷组小鼠每日腹腔注射三七皂苷药液4μL,正常对照组...     

Functional expression of a proliferation-related ligand in hepatocellular carcinoma and its implications for neovascularization

AIM: To detect the expression of a proliferation-related ligand on human hepatocellular carcinoma (HCC) cell lines (SK-Hep1, HLE and HepG2) and in culture medium. METHODS: APRIL expression was analyzed by Western blotting in HCC cell lines. Effects of APRIL to cell count and angiogenesis were analyzed, too. RESULTS: Recombinant human APRIL (rhAPRIL) increased cell viability of HepG2 cells and, in HUVEC, rhAPRIL provided slight tolerance to cell death from serum starvation. Soluble APRIL (sAPRIL) from HLE cells increased after serum starvation, but did not change in SK-Hepl or HepG2 cells. These cells showed down-regulation of VEGF after incubation with anti-APRIL antibody. Furthermore, culture medium from the HCC cells treated with anti-APRIL antibody treatment inhibited tube formation of HUVECs. CONCLUSION: Functional expression of APRIL might contribute to neovascularization via an upregulation of VEGF in HCC.     

Heme oxygenase-1 promotes neovascularization in ischemic heart by coinduction of VEGF and SDF-1

Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with multiple protective functions in cardiovascular systems. Studies have shown that the timely cardiac HO-1 overexpression at acute phase of ischemic infarction (MI) provides protection via its anti-apoptotic and anti-inflammatory effects. Here we demonstrate that a delayed HO-1 transduction mediated by a recombinant adeno-associated virus in ischemic hearts of mice with permanent coronary artery ligation significantly attenuated left ventricular fibrosis and cardiac dysfunctions examined at 4 weeks post MI. HO-1-mediated protection was correlated with enhanced vascularization in the ischemic myocardium. HO-1 gene transfer resulted in a notable increase in the number of c-kit⁺- stem cells recruited to the infarcted area at 10 days after ligation. HO-1-mediated stem cell recruitment was also demonstrated in the heart of non-ischemic mice receiving intravenous infusion of green fluorescent protein-bearing bone marrow stem cells. Additional experiments revealed that vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) were highly induced in HO-1 transduced myocardium. Mononuclear cell infiltration was evident and colocalized with angiogenic factors in the same region. Flow cytometry analysis of the mononuclear cells isolated from HO-1-transduced left ventricles revealed that over 50% of cells expressed CD34, a marker of hematopoietic stem cells and endothelial progenitor cells. VEGF and SDF-1 blockade by neutralizing antibodies significantly attenuated HO-1-mediated neovascularization and protection in infarcted mice. These data suggest that cardiac HO-1 gene transfer post MI provides protection at least in part by promoting neovascularization through inducing angiogenic factors and the recruitment of circulating progenitor/stem cells.     

MIF促进新生微血管生成及其相关基因表达的研究

目的探讨巨噬细胞移动抑制因子(macrophage migration inhibitory factor,MIF)对新生微血管生成及血管内皮生长因子(VEGF)、Smadl 基因表达的影响。方法以体外培养的人血管内皮细胞株 EA.hy926为研究对象,分别用体外血管生成分析试剂盒及免疫组织化学染色法观察 MIF 在体内外对新生微血管生成的作用。通过基因芯片实验检测 MIF 对内皮细胞血管生成相关基因表达的影响,并通过 RT-PCR 检测 MIF 对 VEGF_(165)、Smadl 基因表达的影响。结果 MIF 可以促进人血管内皮细胞在体外形成血管腔,在小鼠体内也能促进新生微血管生成。MIF 可以显著上调血管内皮细胞血管生成基因21个,其中上调 VEGF_(165)、Smadl 基因表达呈剂量依赖性。结论MIF 有促进新生微血管生成的作用,并能促进人血管内皮细胞中 VEGF_(165)、Smadl 基因表达。     

子宫内膜癌组织中内皮抑素的表达及与血管形成的关系

目的:探讨内皮抑素(Endostatin)在子宫内膜样腺癌组织中的表达及其与肿瘤血管形成的关系.方法:应用免疫组织化学方法(MaxVision法)检测66例子宫内膜样腺癌组织及26例增生期子宫内膜组织中内皮抑素的表达及CD34标记的MVD.结果:内皮抑素和MVD在子宫内膜样腺癌组织中高表达(P<0.01),与子宫内膜样腺癌分期有关(P<0.05).结论:内皮抑素检测可作为评价子宫内膜样腺癌生物学参数的参考指标之一.