白藜芦醇对氧诱导鼠视网膜B细胞白血病蛋白2和血管内皮生长因子表达的影响

Effect of resveratrol on the expression of bcl-2 and VEGF in oxygen-induced retinopathy of prematurity in rats

目的探讨白藜芦醇对高氧诱导的早产儿视网膜病变新生鼠视网膜B细胞白血病蛋白2(B-cell leukemia/lymphoma-2,bcl-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法选取鼠龄为7d的Sprague-Dawley(SD)幼鼠60只,分A组(正常对照组)、B组(给氧组)和C(实验组1)、D(实验组2)、E(实验组3)三个实验组,每组12只。A组幼鼠生活在正常氧环境中,B组、C组、D组和E组幼鼠置于氧分压为(75±2)%的氧环境中连续生活5d,建立高氧诱导的早产儿视网膜病变动物模型。C、D、E三个实验组分别予白藜芦醇10mg/(kg·d)、30mg/(kg·d)、60mg/(kg·d)灌胃给药,每天一次,连续5d,所有幼鼠均于17d鼠龄处死。应用Western-blot免疫印迹法分析检测鼠视网膜bcl-2的表达,并以计算机图像分析仪进行分析;用ELISA方法检测鼠视网膜VEGF的表达。结果与A组(正常对照组)比较,B组(给氧组)视网膜bcl-2和VEGF的表达是A组的4倍,两组差异有统计学意义(P<0.01);与B组比较,C、D、E三个实验组视网膜bcl-2和VEGF的表达逐渐减弱,呈剂量依赖关系,不同浓度的白藜芦醇实验组之间存在显著性的差异(P<0.01),三种不同浓度(10mg/kg、30mg/kg、60mg/kg)的白藜芦醇均显著抑制视网膜bcl-2和VEGF的表达,其抑制率分别为11.09%、38.05%、69.76%和3.42%、23.04%、43.69%。结论白藜芦醇可显著抑制高氧诱导的早产儿视网膜病变新生鼠视网膜bcl-2和VEGF表达,可能对早产儿视网膜病变等视网膜新生血管疾病具有治疗作用。

Objective To explore the inhibitory effect of resveratrol on the expression of bcl-2（B-cell leukemia/lymphoma-2） and VEGF（vascular endothelial growth factor） in an animal model of oxygen-induced retinopathy of prematurity.Methods Sixty 7-day-old Sprague-Dawley rats were randomly divided into 5 groups：group A（normal control group）,group B（oxygen-induced group） and three resveratrol-treated groups（group C,group D and group E）.Each group consisted of 12 rats.The rats in group A lived in a normal oxygen environment;the rats in the other groups were placed in an environment with（75±2）% oxygen for 5 days to establish an animal model of oxygen-induced retinopathy of prematurity.The respective doses of resveratrol were given to the three resveratrol-treated groups（10 mg/kg,30 mg/kg and 60 mg/kg） by gastric gavage once a day for 5 days.All rats were sacrificed on the seventeenth day.Western-blot analysis was performed to detect the effect of resveratrol on the expression of bcl-2 in the retinas ,and the picture was analyzed with a computer image analysis meter.ELISA was performed to detect the expression of VEGF in the retinas.Results Compared to group A（normal control group）,the expression of bcl-2 and VEGF in the retinas in group B（oxygen-in-duced group） was strong with a 4-fold increase and the difference was statistically significant（P〈0.01）.Compared to group B（oxygen-induced group）,the expression of bcl-2 and VEGF in the retinas in the three resveratrol-treated groups gradually decreased,showing a dose-dependent effect.The effects of different concentrations of resveratrol at 10 mg/kg,30 mg/kg and 60 mg/kg were statistically significant（P 〈0.01）.The expression of bcl-2 decreased 11.09%,38.05%,and 69.76% and the expression of VEGF decreased 3.42%,23.04% and 43.69% in response to the respective doses of resveratrol.Conclusion Resveratrol can significantly in-hibit the expression of bcl-2 and VEGF in an animal model of oxygeninduced retinopathy of prematurity,which may provide a new approach for the prevention and treatment of retinal neovascular diseases such as retinopathy of prematurity.