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氧诱导视网膜病变鼠模型血管内皮生长因子mRNA的表达 被引量:6

Expression of mRNA of vascular endothelial growth factor in mouse with oxygen-induced retinopathy
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摘要 目的分析氧诱导视网膜病变动物模型血管内皮生长因子(VEGF)基因的调节规律,阐明早产儿视网膜病变(ROP)新生血管形成的可能机制。方法将36只7d龄C57BL/6J幼鼠暴露在(75±2)%浓度的高氧状态下5d,随后在正常氧环境下5d,作为氧诱导模型组;另24只同日龄幼鼠作为正常对照组。采用荧光素血管灌注及视网膜铺片法观察视网膜血管形态;半定量逆转录-聚合酶链反应(RP-PCR)观察各组VEGFmRNA的变化。结果氧诱导模型的视网膜血管形态特征为高氧状态下表层和深层血管的中心区出现无灌注,相对低氧状态下2d后开始出现新生血管,其部位在中周部。RF-PCR结果显示,VEGF的表达与眼内新生血管的发生存在明确的时空对应关系,即高氧状态下,VEGFmRNA转录下降,相对低氧状态下,VEGFmRNA过度转录。结论缺氧是视网膜新生血管发生的主要原因;高氧之后的相对低氧使VEGF表达增加,可能会降低ROP新生血管的发生。 Objective To analyze the regulative rule of mRNA of vascular endothelial growth factor (VEGF) in mice with oxygen-induced retinopathy, and to elucidate the possible mechanism of occurrence of neovascularization in retinopathy of prematurity (ROP). Methods Sixty 7-day-old C57BL/6J mice were divided into oxygen-induced retinopathy group and control group. In oxygen-induced retinopathy group, 36 mice were exposed to 75% oxygen for 5 days and then to room air for 5 days; in control group, 24 mice were raised in room air. Vascular perfusion of fluorescein and retinal stretched preparation were used to observe the morphologic changes of retinal vessels. Reversal transcription- polymerase chain reaction (RT-PCR) was used to observe changes of VEGF mRNA in each group. Results In oxygen-induced retinopathy group, the morphologic characteristics of retinal vessels were the unperfused area at the center of superficial and deep-seated vessels, and the neovascularization appeared at mid-peripheral retina after 2days inrelative hypoxia condition. The results of RT-PCRshowed space-time corresponding relation between expression of VEGF and neovascularization, which meant that the transcription of VEC-F mRNA decreased in hyperxia conditionand increased in relative hypoxia condition. Conclusion Hypoxia is the main reason of occurrence of retinal neovascularization; increased expression of VEGF caused by relative hypoxia after hyperxia might be effective in reducing the occurrence of neovascularization in ROP.
出处 《中华眼底病杂志》 CAS CSCD 北大核心 2005年第5期292-295,共4页 Chinese Journal of Ocular Fundus Diseases
关键词 视网膜病 早产儿 内皮生长因子 基因表达 视网膜新生血管化 疾病模型 动物 Retinopathy of prematurity Vascular endothelial growth factor Gene expression~ Neovascularization Disease models, animal
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  • 1Smith LEH,Wesolowski E,Mclellan A,et al.Oxygen-induced retinopathy in the monse.Invest Ophthalmol vis Sci,1994:35:101-111.
  • 2Simpson DA,Murphy GM,Bhaduri T,et al.Expression of the VEGF gene fmily during retinal vasn-obliteration and hypoxia.Biochem Biophys Res Commun,1999,262:333-340.
  • 3Shima DT,Kuroki M,Deutsch U,et al.The Mouse gene for vascular endothelial growth factor:genomic structure,definition of the transcriptional unit,and characterization of transcriptional and post-transcripional regulatory sequences.J Biol Chem,1996:271:3877-3883.
  • 4Stalmans I,Ng YS,Rohan R,et al.Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms,JClin Invest,2002,109:327-336.
  • 5McColm JR,Geisen P,Hartnett ME.VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations betwenn hyperoxia and hypoxia:relevance to clinical ROP.Mol Vis,2004,10:512-520.

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