多巴胺对氧诱导视网膜病变小鼠视网膜新生血管的影响  

Effect of dopamine on retinal neovascularization in oxygen-induced retinopathy mice

作　　者：张凤一 高洪莲[2] 邱宇 崔钰莹 李童 王亚彤 张磊[1] ZHANG Fengyi;GAO Honglian;QIU Yu;CUI Yuying;LI Tong;WANG Yatong;ZHANG Lei(Department of Ophthalmology,the Affiliated Hospital of Binzhou Medical University,Binzhou 256600,Shandong Province,China;Medical Research Center,the Affiliated Hospital of Binzhou Medical University,Binzhou 256600,Shandong Province,China)

机构地区：[1]滨州医学院附属医院(第一临床医学院)眼科,山东省滨州市256600 [2]滨州医学院附属医院(第一临床医学院)医学研究中心,山东省滨州市256600

出　　处：《眼科新进展》2023年第1期25-29,共5页Recent Advances in Ophthalmology

摘　　要：目的观察多巴胺(DA)及多巴胺D2受体(DRD2)在氧诱导视网膜病变(OIR)小鼠模型中对视网膜新生血管的作用。方法随机将180只小鼠分为空白组、OIR组、NaCl组、DA组、Quinpirole(DRD2激动剂)组、Spiperone(DRD2抑制剂)组,每组30只。空白组小鼠在正常环境中饲养,其他各组小鼠在7 d龄时于高氧环境中饲养5 d,于小鼠12 d龄时返回正常环境中,OIR组不做药物干预,NaCl组、DA组、Quinpirole组分别于小鼠右眼玻璃体内注射8.5 g·L^(-1)NaCl、15 mmol·L^(-1)的DA溶液、602μmol·L^(-1)的Quinpirole溶液,Spiperone组小鼠右眼玻璃体内依次注射154μmol·L^(-1)的Spiperone溶液和15 mmol·L^(-1)的DA溶液各1μL。小鼠17 d龄时处死,摘取右侧眼球进行后续实验。采用苏木精-伊红(HE)染色和视网膜铺片检查各组小鼠视网膜新生血管情况;采用Q-PCR和Western blot检测各组小鼠视网膜中血管内皮生长因子(VEGF)mRNA和蛋白的相对表达量。结果OIR组小鼠视网膜中突破内界膜的血管内皮细胞核数、新生血管面积占比、VEGF mRNA和蛋白相对表达量均明显高于空白组(均为P<0.05);NaCl组和Spiperone组小鼠视网膜中突破内界膜的血管内皮细胞核数、新生血管面积占比、VEGF mRNA和蛋白相对表达量与OIR组相比差异均无统计学意义(均为P>0.05);与OIR组相比,DA组小鼠视网膜中突破内界膜的血管内皮细胞核数、新生血管面积占比、VEGF mRNA和蛋白相对表达量均降低(均为P<0.05);与DA组相比,Quinpirole组小鼠视网膜中突破内界膜的血管内皮细胞核数、新生血管面积占比、VEGF mRNA和VEGF蛋白相对表达量均降低(均为P<0.05)。结论DA可以通过激活DRD2途径来抑制VEGF的表达,从而减少OIR小鼠视网膜新生血管的产生。Objective To observe the effects of dopamine(DA)and dopamine receptor D2(DRD2)on retinal neovascularization in the mouse model of oxygen-induced retinopathy(OIR).Methods Totally 180 mice were randomly divided into 6 groups:blank group,OIR group,NaCl group,DA group,Quinpirole(DRD2 agonist)group and Spiperone(DRD2 inhibitor)group,with 30 mice in each group.The mice in the blank group were raised in a normal environment,while other groups of mice were continuously raised in a hyperoxia environment for 5 days at 7 days old,and then returned to a normal environment at 12 days old.The mice in the OIR group did not receive any drug intervention,and the mice in the NaCl group,DA group and Quinpirole group were injected with 1μL of 8.5 g·L^(-1)NaCl,15 mmol·L^(-1)DA solution and 602μmol·L^(-1)Quinpirole solution into the vitreous body of right eyes,respectively.The mice in the Spiperone group were injected with 154μmol·L^(-1)Spiperone solution and 15 mmol·L^(-1)DA solution into the vitreous body of right eyes.The mice were sacrificed at 17 days old,and the right eyeballs were removed for follow-up experiments.The retinal neovascularization of mice in each group was examined by Hematoxylin-eosin staining and retinal stretched preparation.The relative expressions of vascular endothelial growth factor(VEGF)messenger ribonucleic acid(mRNA)and protein in the retina of mice in each group were detected by quantitative PCR and Western blot,respectively.Results The number of endothelial cell nuclei that break through the inner limiting membrane,the ratio of neovascularization area,the relative expressions of VEGF mRNA and protein in the OIR group were significantly higher than those in the blank group(all P<0.05);compared with the OIR group,there were no significant differences in the number of endothelial cell nuclei that break through the inner limiting membrane,ratio of neovascularization area,VEGF mRNA and protein relative expression levels in the NaCl group and Spiperone group(all P>0.05);compared with the OIR group,th

关 键 词：血管内皮生长因子 视网膜新生血管 多巴胺 氧诱导视网膜病变模型 小鼠 

分 类 号：R774.1[医药卫生—眼科]