血管内皮生长因子、色素上皮衍生因子在酸中毒诱导的早产儿视网膜病大鼠动物模型中的表达

Expression of VEGF and PEDF in a rat model of acidosis-induced retinopathy

目的建立酸中毒诱导早产儿视网膜病(ROP)大鼠动物(AIR)模型,观察血管内皮生长因子(VEGF)、色素上皮衍生因子(PEDF)在正常新生大鼠及ROP模型大鼠视网膜中的表达变化规律,探讨二者表达变化与酸中毒的关系、对视网膜血管发育的作用以及在酸中毒诱导ROP进程中的作用。方法1日龄SD新生大鼠随机分为酸中毒诱导模型组(ROP组)和正常对照组。应用逆转录-聚合酶链反应(RT-PCR)测定全视网膜VEGF、PEDF的mRNA水平。结果RT-PCR结果显示,8日龄ROP大鼠VEGF mRNA转录水平明显低于C组(P<0.05),停止管饲NH4Cl后ROP组VEGFmRNA转录水平逐渐增强,10日龄、13日龄ROP大鼠视网膜VEGF mRNA转录水平明显上升,较对照组明显增强(P<0.05)。5日龄、8日龄ROP大鼠视网膜PEDF mRNA表达水平明显高于对照组(P<0.05),而在停止管饲NH4Cl的10日龄、13日龄视网膜中其表达水平低于对照组(P<0.05)。在实验过程中PEDF mRNA的表达趋势与VEGF相反;ROP组大鼠在酸中毒期间其VEGF mRNA/PEDF mRNA之值明显降低,停止管饲NH4Cl后,VEGF mRNA/PEDF mRNA之值升高,与对照组相比差异有显著性(P<0.05)。结论酸中毒使VEGF mRNA表达下调,PEDF mRNA表达上调;停止管饲NH4Cl后二者表达的影响与酸中毒时相反;VEGF、PEDF可能在视网膜正常血管发育及ROP的新生血管化进程中起重要作用,二者比率变化过程与视网膜新生血管发展进程有关。

Objective To establish an animal model of acidosis-induced retinopathy （AIR）, analyze the expression of vascular endothelial growth factor（VEGF） and pigment epithelium-derived factor（PEDF） in a rat model of acidosis-induced retinopathy and to elucidate the action of VEGF and PEDF in the process of neovascularization in retinopathy of prematurity （ROP）. Methods Newborn Sprague-Dawley rats were randomly divided into acidosis-induced retinopathy group （ROP group） and control group. Reversal transcription-polymerase chain reaction （RT-PCR） was used to quantify the changes of VEGF mRNA and PEDF mRNA in each group. Results RT-PCR showed that the transcription of VEGF mRNA of ROP group at the 8th was significantly lower than control group, and started to gradually increas after stopping the NH4 Cl feeding. Especially on the 10th and 13th day,the transcription of VEGF mRNA of ROP group is much higher than the control group. The changes of PEDF mRNA were opposite to VEGF mRNA. The retina VEGF/PEDF mRNA retio of ROP group decreased significantly than the control group during asidosis, and increased when tubal feeding of NH4 Cl was stopped. Conclusions The periods of acidosis result in down-regulation of VEGF and up-regula- tion of PEDF. The time course of the VEGF/PEDF ratio change correlats with the progression of retinal neovaseularization. These results suggest that an unbalance between angiogenic stimulators and inhibitors may contribute to retinal neovascularization. The abnormal retina VEGF/PEDF retio may play an important role in the development of neovascularization in ROP.