金雀异黄素对血管增生性视网膜病变小鼠中VEGF表达的影响
- 文献标志码:
- A
- 摘要:
- 目的研究相对缺氧对小鼠视网膜血管内皮生长因子( vascular endothelial growth factor, VEGF) 表达的诱导作用,以及金雀异黄素( genistein, Gen) 对其表达的影响和机理。方法制作缺氧小鼠模型,采用视网膜切片计数视网膜血管的增生,免疫荧光法检测视网膜中VEGF的表达,分析不同Gen浓度(0、50、100、200mg/kg)对缺氧致血管增生性视网膜病变小鼠的VEGF表达的影响。结果正常对照组小鼠视网膜切面有少量血管内皮细胞核,0剂量组(相对缺氧组)视网膜切片中突破内界膜的血管内皮细胞核数较对照组显著增加(P<0.001),提示相对缺氧诱导视网膜血管新生,表明动物模型制作成功。给药组突破内界膜的血管内皮细胞核数均较相对缺氧组减少,并且呈剂量依赖性,提示Gen可抑制缺氧诱导的视网膜血管新生。与对照组相比,相对缺氧组小鼠视网膜内层VEGF的表达明显增强;Gen给药组VEGF的表达较相对缺氧组减弱。结论Gen可抑制缺氧诱导的VEGF的表达,提示Gen 对视网膜新生血管的形成具有预防和潜在的临床价值。
参考文献/References:
1Miller JW.Vascular endothelial growth factor and ocular neovascularization\[J\].Am J Pathol,1997,151(1):13—23.2Polkowski K,Mazurek AP.Biological properties of genistein. A review of in vitro and in vivo data\[J\].Acta Pol Pharm,2000,57(2):135—155. 3Andrew p,Levy,Nina S,Levy Mark A.Goldberg. Posttranscriptional regulation of vascular endothelial growth factor by hypoxia\[J\].J Bio Chem,1996,271(5):2746—2753.4Pages G,Milanini J,Richard DM,et al.Signaling angiogenesis via p42/p44 MAP kinase cascade\[J\].Ann N Y Acad Sci,2000,902:187—200.5Marti HJ,Bernaudin M,Bellail A,et al.Hypoxiainduced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia\[J\].A M J Pathol.2000,156(3): 965—976.6Guang L Wang,Gregg L Semenza.Purification and characterization of hypoxiainducible factor 1\[J\].Biochem J,1995,270:1230—1237.7Wang G L.Hypoxiainducible factor 1 is a basichelixloophelixPAS heterodimer regulated by cellular O2 tension\[J\].Proc Natl Acad Sci USA, 1995,92:5510—5514.8Gerber HP,Condorelli F,Park J,et al.Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes.Flt1, but not Flk1/KDR, is upregulated by hypoxia\[J\].J Biol Chem,1997,272(38):23659—23667.9Constantinou A,Huberman E.Genistein as an inducer of tumor cell differentiation: possible mechanisms of action\[J\].Proc Soc Exp Biol Med,1995,125:109—115.
备注/Memo
Email:zyfpw@live.cn