生长发育迟滞与鼠视网膜病变发生的相关研究

Correlation of intra-,extrauterine malnutrition and retinopathy of prematurity in mice

目的探讨生后生长发育迟滞对鼠视网膜的影响。方法将怀孕18 d的C57BL/6母鼠随机分为正常对照组、生长发育迟滞组、氧诱导视网膜病(oxygeninduced retinopathy,OIR)组、生长发育迟滞+OIR组。正常对照组母鼠予正常饮食;生长发育迟滞组母鼠予等热卡低蛋白饮食,持续至幼鼠出生21 d;OIR组建立OIR模型;生长发育迟滞+OIR组予生长发育迟滞及OIR联合诱导。于出生14 d、21 d检测血糖、胰岛素和胰岛素样生长因子-1(insulin-like growth factor,IGF-1)的变化。于生后14 d、21 d留取视网膜组织,检测精氨酸2活性及血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达。出生70 d,应用视网膜电流图评估视网膜功能。结果生长发育迟滞组、生长发育迟滞+OIR组小鼠出生体质量明显低于其他两组(均为P<0.05),生后14 d、21 d,生长发育迟滞组、生长发育迟滞+OIR组小鼠体质量、胰岛素、IGF-1值、VEGF在视网膜表达均显著低于正常对照组(均为P<0.05),而精氨酸2活性显著高于正常对照组(均为P<0.05)。OIR组、生长发育迟滞组、生长发育迟滞+OIR组小鼠视网膜毛细血管密度指数增加,而以生长发育迟滞+OIR组小鼠增加最显著。生后70 d时OIR组、生长发育迟滞组小鼠视网膜电流图反应减弱,RmP 2振幅(双极细胞)及8 Hz频闪振幅(R8:视网膜内功能)显著减小,且生长发育迟滞+OIR组小鼠变化更加明显。结论生长发育迟滞小鼠影响IGF-1、VEGF的表达及精氨酸2的活性,对视网膜病的发生有显著促进作用。

Objective To investigate the effects of growth retardation af- ter preterm birth on retinopathy of prematurity. Methods The pregnant 18 days C57BL / 6 mice were randomly divided into normal control group, growth retardation group,oxygen-induced retinopathy （OIR） group,and growth retarda- tion ＋ OIR group. The pregnant mice in normal control group were only given the normal diet. The pregnant mice in growth retardation group were given the iso- caloric low-protein diet, continued to 21 days for pups after birth, to induce growth retardation pups. For OIR group pups, the OIR models were established in the mother and pups. The pregnant mice in growth retardation ＋ OIR group were given growth retardation and OIR models were established. At 14 days and 21 days after birth, the blood glucose, insulin, and insnlin-like growth factor-1 （IGF-1） were tested. The arginine 2 and vascular endothelial growth factor （VEGF） in retinal tissue were detected. At 70 days after birth, electroretinogram （ERG） was used to assess retinal function. Results The birth weight of the growth retardation group and growth retardation ＋ OIR group were significantly lower than those of other two groups （ all P 〈 0.05 ）, at 14 days and 21 days after birth,the weight, insulin, IGF-1 and VEGF in the growth retardation group and growth retardation ＋ OIR group were significantly lower than those of the normal control group （ all P 〈 0.05 ）, but arginine 2 was much higher （ all P 〈 0.05 ）. The retinal capillary density index significantly increased in OIR group, growth retar- dation group and growth retardation ＋ OIR group, especially in growth retarda- tion ＋ OIR group. At 70 days of mice after birth, ERG analysis was done for all groups, ERG response weakened in growth retardation group and OIR group, and RmP2 amplitude （ bipolar cells） and 8 Hz flicker amplitude （ R8 ：the retina func- tion） was significantly reduced. ERG response was the most weakest in growth retardation ＋ OIR groups. Conclusion Growth retardation after birth for pre- maturity can effect the expression of IGF-1, VEGF and arglnine 2, and significant- ly effect the occurrence of retinopathy of prematurity.