黄芪注射液载入修饰胶原促进血管再生的研究

目的:将黄芪载入胶原支架内,通过对胶原支架进行修饰,观察黄芪是否具有促血管生成活性及探讨可能的生物学机制.方法:将5,10μL黄芪注射液载入修饰后的胶原内,通过鸡胚绒毛尿囊膜(CAM,Chicken Chorioallantoic Membrane)实验模型,从胶原周围微血管再生数量、胶原内血红蛋白含量、胶原干重、CD_(34)抗原免疫组化标记等指标来考察黄芪注射液对肝素修饰后胶原促血管再生的作用.结果:黄芪联合肝素修饰后的胶原能够产生与血管内皮生长因子相当的疗效,血管计数、胶原血红蛋白含量、CD_(34)的表达均显著性增加(P＜0.01,与单纯胶原组比较);与单纯胶原组相比,胶原+黄芪10ul组胶原干重显著增加(P＜0.05).结论:黄芪注射液载入修饰后的胶原具有良好的促血管再生作用.     

黄芪注射液对稳定型心绞痛患者血浆血管内皮生长因子水平的影响

目的观察黄芪注射液治疗冠心病稳定型心绞痛患者的疗效及对血浆血管内皮生长因子的影响。方法将100例患者随机分为治疗组和对照组,对照组采用常规治疗,治疗组加用黄芪注射液静脉输注,3周后观察两组的疗效和治疗前后血浆血管内皮生长因子水平的变化。结果治疗组治疗后血浆血管内皮生长因子较前明显升高（P〈O．01）,治疗组的临床疗效优于对照组（P〈O．05）。结论黄芪注射液可通过升高血浆血管内皮生长因子水平,而达到更好地治疗冠心病的目的。     

黄芪多糖修饰胶原促血管新生的实验研究

目的：研究黄芪多糖修饰胶原的促血管新生作用,并对其作用及发生机制进行初步探讨。方法：在鸡胚绒毛尿囊膜（CAM）模型及SD大鼠模型中观察新生微血管密度、胶原中血红蛋白及肉芽组织中羟脯氨酸含量验证黄芪多糖修饰胶原的促血管新生作用,并对最佳剂量进行观察。通过VEGF及整合素蛋白αvβ3的表达探讨促血管新生作用的机制。结果：CAM模型中,20μg/mL黄芪多糖＋胶原组微血管明显高于其他各组;大鼠模型中,胶原中血红蛋白含量及肉芽组织中羟脯氨酸含量明显高于对照组;肉芽组织中VEGF及整合素蛋白αvβ3表达明显。结论：20μg/mL黄芪多糖修饰胶原能明显促进血管新生,其发生机制与VEGF及整合素蛋白αvβ3的表达相关。     

健脾活血法对类风湿性关节炎患者促肾上腺皮质激素与血管内皮生长因子水平的影响

目的：观察健脾活血法对类风湿性关节炎患者促肾上腺皮质激素和血管内皮生长因子水平的影响。方法：将60例患者按照随机数字表法分为中医组和西医组,每组各30例。中医组给予健脾活血法辨证治疗,西医组给予消炎痛联合甲氨蝶呤治疗,测定治疗前后患者血清促肾上腺皮质激素和血管内皮生长因子水平,评价疗效和安全性。结果：中医组有效率为96．7％,西医组有效率为83．3％,两组有效率比较,差异具有统计学意义（P〈0．05）。两组治疗后血清促肾上腺皮质激素水平均较治疗前明显升高,血清血管内皮生长因子较治疗前明显降低,差异具有统计学意义（P〈0．05）,中医组与西医组治疗后比较,差异具有统计学意义（P〈0．05）。结论：健脾活血法能够显著提升类风湿性关节炎患者血清促肾上腺皮质激素水平,降低血管内皮生长因子水平。     

促愈汤对胃溃疡患者胃泌素及胃黏膜血管内皮生长因子水平的影响

目的:探讨促愈汤对胃溃疡患者胃泌素及胃黏膜血管内皮生长因子水平的影响。方法:选取胃溃疡患者60例,随机分为治疗组和对照组各30例,对照组患者进行常规西药治疗,治疗组患者在此基础上加服促愈汤进行治疗,比较两组患者的治疗效果。结果:经过治疗,治疗组在降低血胃泌素含量方面与对照组无显著区别(P0.05),在提高血管内皮生长因子血液浓度以及胃黏膜血管内皮生长因子表达水平方面较对照组效果更为显著,差异具有统计学意义(P0.05)。结论:促愈汤对血胃泌素含量无显著影响,其提高胃溃疡愈合质量主要与提高血管内皮生长因子水平和促进胃黏膜血管内皮生长因子表达有关。     

穿山龙总皂苷对胶原诱导关节炎大鼠滑膜血管内皮生长因子、血管生成素-2及受体Tie-2表达的影响

 目的 观察穿山龙总皂苷对胶原诱导关节炎大鼠滑膜血管内皮生长因子、血管生成素2及其受体Tie-2的影响,探讨穿山龙总皂苷治疗类风湿关节炎的抗血管新生机制。方法 建立胶原诱导关节炎大鼠模型,动物随机分为空白对照组、胶原诱导关节炎模型组、穿山龙总皂苷组、雷公藤多苷组（作为阳性对照组）和薯蓣皂苷元组,采用实时荧光定量PCR方法检测大鼠膝关节滑膜血管内皮生长因子mRNA的表达情况,采用免疫组织化学方法检测大鼠膝关节滑膜血管生成素-2及其受体Tie-2蛋白的表达。结果 胶原诱导关节炎模型组大鼠滑膜血管内皮生长因子mRNA、血管生成素-2及Tie-2蛋白表达明显高于空白对照组(P<0.01),经穿山龙总皂苷、雷公藤和薯蓣皂苷元治疗后血管内皮生长因子mRNA和血管生成素-2表达均低于胶原诱导关节炎模型组(P<0.01);而Tie-2表达呈降低趋势,差异无统计学意义。穿山龙总皂苷组血管内皮生长因子mRNA表达比雷公藤组和薯蓣皂苷元组血管内皮生长因子mRNA明显降低(P<0.01)。结论 穿山龙总皂苷可能通过降低滑膜血管内皮生长因子mRNA、血管生成素-2及Tie-2的表达,抑制滑膜血管新生,从而对类风湿关节炎发挥治疗作用。     

黄芪桂枝五物汤加减治疗脑梗死临床观察

目的 观察黄芪桂枝五物汤加减治疗脑梗死的临床疗效.方法 将患者随机分为两组,治疗组给予西医常规治疗联合黄芪桂枝五物汤加减,对照组给予西医常规治疗;比较两组神经功能缺损程度评分、临床总有效率以及其对血清肿瘤坏死因子α(TNF-α)浓度的影响.结果 治疗组疗效优于对照组.结论 方剂黄芪桂枝五物汤加减治疗脑梗死临床疗效可靠,其机制可能与下调促炎因子表达,减轻炎症反应,减少血管内皮损伤,保护脑组织细胞有关.     

中药改善心肌梗死促血管新生机制的研究进展

心肌梗死是临床常见病,属中医“胸痹”“心痛”范畴,血管新生、血运重建是治疗心肌梗死的有效途径。中药在促血管新生、改善心肌缺血方面具有独特优势和潜力,研究表明中药复方、单体及有效成分可通过不同靶点、不同途径介导心肌梗死后促血管新生的作用机制。本文通过梳理文献总结出中药具有增强干细胞血管修复与新生能力,可以调控促血管生成因子分泌及其受体表达,并且靶向调控外泌体传递与血管新生相关的miRNA,激活下游信号,增加内皮细胞存活、迁移、成管能力,提升促血管新生相关基因和蛋白表达,还可以激活血管内皮生长因子/内皮型一氧化氮合成酶信号通路,调控微血管生成过程和间充质干细胞的Notch信号通路,活化蛋白激酶D1/缺氧诱导因子-1α/血管内皮生长因子信号通路,抑制沉默信息调节因子3/β-连环蛋白/过氧化物酶体增殖物激活受体γ信号通路等介导心肌梗死区域的血管再生功能。后续还需深入探讨中药促血管新生的作用机制及药效物质基础,为中医药防治缺血性心脏病的再生医学研究提供依据。     

解毒散结方联合化疗治疗晚期胃癌疗效及对患者血管内皮生长因子和受体的影响

目的:探讨解毒散结方联合化疗对晚期胃癌患者疗效及对血清血管内皮生长因子-A(VEGF-A)、血管内皮生长因子-D(VEGF-D)、血管内皮生长因子受体-1(VEGFR-1)的影响。方法:选取102例晚期胃癌患者为研究对象,以随机数字表法分为对照组(替吉奥联合奥沙利铂化疗)和观察组(对照组基础上联合解毒散结方治疗),每组均为51例,两组均治疗12周。观察两组临床疗效、治疗前后中医症候评分、血清VEGF-A、VEGF-D、VEGFR-1水平以及治疗期间不良反应发生情况。结果:治疗12周后两组疗效等级分布比较差异显著(P<0.05),且观察组的总有效率高于对照组(P<0.05); 治疗12周后两组患者中医症候评分均降低(P<0.05),且观察组更低(P<0.05); 治疗12周后,两组血清VEGF-A、VEGFR-1水平均降低(P<0.05),两组血清VEGF-D水平均升高(P<0.05),且观察组血清VEGF-A、VEGFR-1水平更低(P<0.05),观察组血清VEGF-D水平更高(P<0.05); 两组不良反应发生率相近(P>0.05)。结论:解毒散结方联合替吉奥联合奥沙利铂化疗用于治疗脾胃虚弱、瘀毒蕴结证晚期胃癌患者能够改善临床症状及血管内皮生长因子水平,疗效显著。     

心肌缺血中血管内皮生长因子的临床研究述要

血管内皮生长因子(VEGF)是一种特异作用于血管内皮的促有丝分裂原,具有促进内皮细胞分裂、增殖和迁移,从而加速血管再生,增加血管通透性,建立有效的侧支循环.其在冠心病的治疗中所起的作用日前倍受关注,有潜力成为治疗冠心病的又一新的方法.     

The Role of Traditional Chinese Medicines in Osteogenesis and Angiogenesis

The article aims to review various Traditional Chinese Medicines (TCMs) with both osteogenic and angiogenic effects, alone and in combination, and to consider whether these TCMs promote osteogenesis via angiogenesis and vascular endothelial growth factor (VEGF). Each of the TCMs involving in osteogenesis was searched through PubMed and CBMdisc using its Latin name and English name, and keywords such as ‘osteogenesis’, ‘bone’, ‘osteoblast’, ‘angiogenesis’, ‘VEGF’ were used. A total of 241 articles were screened from PubMed and CBMdisc. The articles were only chosen if they discussed the relationship of the TCMs with bone formation and/or angiogenesis. Twenty‐seven articles were chosen, of which 16 were in English and 11 were in Chinese with English abstract. As a result, the TCMs (Danshen or Salvia miltiorrhiza Bunge, Danggui or Angelica sinensis, Astragalus membranaceus Bunge or Huangqi, and Ge Gan or Puerarin radix) that have a relationship with both osteogenesis and angiogenesis were screened out. It is found that the aforementioned TCMs enhance angiogenesis and osteogenesis. They show a positive effect on bone formation, and the possible mechanisms may be related to their ability to promote angiogenesis via an effect on substances such as VEGF. Copyright © 2013 John Wiley & Sons, Ltd.     

黄芪卫矛合剂调节糖尿病肾病大鼠肾组织细胞因子平衡的研究

目的:观察黄芪卫矛合剂对糖尿病肾病模型大鼠肾组织VEGF、TSP-1和NO、ET-1的影响,探讨黄芪卫矛合剂治疗糖尿病肾病的作用机制。方法:采用单侧肾切除并链脲佐菌素尾静脉注射建立大鼠糖尿病肾病模型,造模成功后,大鼠随机分为假手术组、糖尿病肾病组、糖尿病肾病+黄芪卫矛合剂组和糖尿病肾病+氯沙坦钾组,共观察12周。用免疫组织化学染色法观察大鼠肾小球内血管内皮细胞生长因子(VEGF)和血小板反应蛋白1(TSP-1)的表达,硝酸还原化学比色法测定肾组织NO的含量,放射免疫法测定肾组织ET-1含量。结果:假手术组肾小球内VEGF强表达,TSP-1偶见有表达;糖尿病肾病大鼠肾小球内VEGF明显减弱,而TSP-1表达明显增多(与假手术组比较P<0.01);各用药组VEGF表达较模型组有明显增多,TSP-1表达均明显减少,与模型组比较有显著性或非常显著性差异(P<0.05,P<0.01)。两用药组之间两两比较没有显著性差异(P>0.05)。糖尿病肾病模型组大鼠肾组织内NO含量较假手术组明显降低(P<0.01),ET-1含量较假手术组明显升高(P<0.05),黄芪卫矛合剂组大鼠肾组织内NO含量明显增加,ET-1含量明显降低,与模型组比较有显著性差异(P<0.05);氯沙坦钾组肾组织NO和ET-1含量与模型组比较无显著性差异(P>0.05)。结论:黄芪卫矛合剂可增加肾小球内VEGF表达,降低TSP-1表达,提高肾组织中NO含量,降低ET-1含量,调节与肾小球内皮细胞密切相关细胞因子VEGF、TSP-1和NO、ET-1的平衡,从而保护肾组织微小血管内皮细胞,促进毛细血管和小血管再生和重建。是黄芪卫矛合剂防治糖尿病肾病的重要作用机制之一。同时证明了黄芪与卫矛配伍科学性和有效性,也是中医气血关系理论的进一步验证。     

Flavonoids inhibit angiogenic cytokine production by human glioma cells

VEGF and TGF-β1 are cytokines that stimulate tissue invasion and angiogenesis. These factors are considered as molecular targets for the therapy of glioblastoma. Bevacizumab, a recombinant humanized monoclonal antibody developed against VEGF, inhibits endothelial cell proliferation and vessel formation. Flavonoids obtained from Dimorphandra mollis and Croton betulaster have been described as proliferation inhibitors of a human glioblastoma derived cell line. VEGF and TGF-β1 levels were dosed by ELISA in a GL-15 cell line treated with bevacizumab and also with the flavonoids rutin, 5-hydroxy-7,4'-dimethoxyflavone, casticin, apigenin and penduletin. Rutin reduced the VEGF and TGF-β1 levels after 24 h but not after 72 h. The other flavonoids significantly reduced TGF-β1 production. Bevacizumab reduced only the VEGF levels in the supernatant from GL-15 cultures. These results suggest that the flavonoids studied, and commonly used in popular medicine, present an interesting subject of study due to their potential effect as angiogenic factor inhibitors.     

Promotion of direct angiogenesis in vitro and in vivo by Puerariae flos extract via activation of MEK/ERK‐, PI3K/Akt/eNOS‐, and Src/FAK‐dependent pathways

Puerariae flos has been used for oriental herbal medicine; however, its angiogenic effect has not been elucidated. We found that the extract from Puerariae flos (PFE) increased in vitro angiogenic events, such as endothelial cell proliferation, migration, and tube formation, as well as in vivo neovascularization. These events were followed by the activation of multiple signal modulators, such as extracellular signal‐regulated kinase (ERK), Akt, endothelial nitric oxide synthase (eNOS), nitric oxide production, p38, Src, and focal adhesion kinase (FAK), without increasing vascular endothelial growth factor (VEGF) expression. Inhibition of ERK, Akt, and eNOS suppressed PFE‐induced angiogenic events, and inhibition of p38 and Src activities blocked PFE‐induced endothelial cell migration. PFE did not affect the expression of intracellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 and transendothelial permeability, which are involved in the adverse effects of the well‐known angiogenic inducer VEGF. These results suggest that PFE directly stimulates angiogenesis through the activation of MEK/ERK‐, phosphatidylinositol 3‐kinase/Akt/eNOS‐, and Src/FAK‐dependent pathways, without altering VEGF expression, vascular inflammation, and permeability in vitro and in vivo and may be used as a therapeutic agent for ischemic disease and tissue regeneration. Copyright © 2009 John Wiley & Sons, Ltd.     

Radix Astragali extract promotes angiogenesis involving vascular endothelial growth factor receptor‐related phosphatidylinositol 3‐kinase/Akt‐dependent pathway in human endothelial cells

Angiogenesis plays an important role in a wide range of physiological processes and many diseases are associated with dysregulation of angiogenesis. Radix Astragali, commonly used in traditional Chinese medicine, is a potential candidate for treating such diseases. However, the biological effects of Radix Astragali on angiogenesis and its underlying mechanisms are yet to be elucidated fully. This study describes the angiogenic effects of Radix Astragali extract (RAE) on human umbilical vein endothelial cells (HUVEC) in vitro. It was shown that RAE treatment stimulated HUVEC to proliferate. A significant increase in migration was observed in RAE‐treated HUVEC using the wound healing migration assay. In addition, a significant increase in the number of branching points was observed during endothelial cell capillary formation after RAE treatment. It was shown that RAE enhances vascular endothelial growth factor (VEGF) mRNA expression, and that a specific blocker of VEGF receptor 2 (KDR/Flk) inhibited the RAE‐induced HUVEC proliferation. In addition, a decrease in the RAE‐induced HUVEC proliferation was observed after treatment with inhibitors of phosphatidylinositol 3‐kinase (PI3K), Akt and endothelial nitric oxide synthase (eNOS). Taken together, these data suggest that RAE is a potent stimulator of angiogenesis and that its pro‐angiogenic effects involve the VEGF‐KDR/Flk and PI3K‐Akt‐eNOS pathways. Copyright © 2009 John Wiley & Sons, Ltd.     

Gallic acid is partially responsible for the antiangiogenic activities of Rubus leaf extract

An aqueous extract of leaves from Rubus suavissimus S. Lee (Rosaceae) or sweet leaf tea was tested for antiangiogenic activity in a human tissue-based fibrin-thrombin clot angiogenesis assay. Further fractionation of this crude extract was performed and the antiangiogenic effect of individual fractions was assessed. The extract was also tested for its oral bioavailability by using the serum of normal rats gavaged with the extract in the assay. At a 0.1% w/v concentration, the extract inhibited initiation of the angiogenic response and subsequent neovessel growth from samples that had already initiated an angiogenic response. Two subfractions of the extract showed significant inhibition of angiogenesis at 0.1% w/w. Gallic acid was elucidated as one of the active angiogenesis inhibitors in one fraction. A 1 mm concentration of gallic acid totally inhibited angiogenesis. In the form of leaf extract, a one-tenth concentration produced the same total inhibition as pure gallic acid. The 10-fold difference in potency suggests the presence of other active compounds contributing to the overall antiangiogenic effect of the extract. The oral absorption of this extract was tested by using serum from rats given the extract orally (gavage) in the angiogenesis assay system. The serum of rats orally administered the sweet leaf tea extract at doses of 0.1% w/w and 0.3% w/w did not significantly inhibit angiogenesis. However, the serum of rats injected intraperitoneally at a dose of 0.1% w/w caused a 41% inhibition of angiogenesis compared with saline injected controls. These preliminary results warrant further bioassay directed identification of other responsible compounds.     

麝香酮干预血瘀证乳腺癌组织血管生成相关因子表达研究

目的:观察麝香酮对血瘀证裸鼠乳腺癌组织血管生成相关因子表达影响.方法:应用乳腺癌MDA231细胞株,经培养传代后,种植给提前血瘀证造模成功的裸鼠,并采用麝香酮灌胃干预,以免疫组化方法检测裸鼠血管内皮细胞生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)的表达.结果:与模型对照组比较,麝香酮干预的肿瘤组织VEGF、...     

鳖甲煎丸对HUVEC增殖及HepG2中VEGF表达的影响

目的:通过研究鳖甲煎丸对人脐静脉血管内皮细胞(human umbilical vascular endothelial cell,HUVEC)增殖及肝癌细胞系HepG2中血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响,探讨其抗肝细胞癌血管生成的机制。方法:将24只6周龄Wistar大鼠随机分为3组(8只/组),分别以临床剂量20,10倍的鳖甲煎丸水溶液及生理盐水ig 3d,3 d后采血,离心,获取血清。用含有不同浓度HepG2培养上清的条件培养基培养HUVEC,48 h后用MTT比色法检测HUVEC的增殖情况并确定条件培养基的最适浓度。用该浓度的条件培养基培养HUVEC,分别于48,72 h后采用MTT比色法检测药物血清对HUVEC增殖的影响。用含药血清培养HepG2,48 h后采用ELISA方法检测培养液上清中VEGF的浓度,采用qRT-PCR法检测VEGF mRNA的表达情况。结果:鳖甲煎丸高、中剂量组10%药物血清能够显著抑制HUVEC的增殖,这种抑制作用具有浓度和时间依赖性。鳖甲煎丸高、中剂量10%药物血清组中VEGF浓度与VEGF mRNA表达水平均明显下降,并且下降程度与药物浓度有关。结论:鳖甲煎丸能够抑制HUVEC的快速增殖并且显著地降低HepG2中VEGF的表达水平。研究表明鳖甲煎丸在抗肝细胞癌血管生成方面具有一定作用。     

麝香保心丸对鸡胚绒毛尿囊膜及培养的血管内皮细胞的促血管生成作用

目的：探讨麝香保心丸在鸡胚绒毛尿囊膜模型及培养的微血管内皮细胞系统中的促血管生成作用。方法：分别以重组碱性成纤维细胞生长因子（bFGF,贝复济）和生理盐水为阳性和阴性对照,作用于绒毛尿囊膜（chrioallantoic membrane,CAM),通过一级、二级血管计数,初步评价麝香保心丸的促血管生成活性;并通过观察它对培养的牛肾上腺微血管内皮细胞增殖及管腔结构形成的影响,验证其促血管生成效应;同时检测麝香保心丸作用于培养的人脐静脉内皮细胞血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF)的mRNA表达及其上清液中VEGF、bFGF含量,初步探索其作用机理。结果：麝香保心丸组CAM上血管数比生理盐水组明显增加;麝香保心丸组内皮细胞及管腔数目均较生理盐水组明显增多,前者细胞表达VEGF和bFGF mRNA明显增高,上清液中VEGF和bFGF含量明显增多。结论：麝香保心丸能促进CAM及培养的微血管内皮细胞的血管生成。