多巴胺对氧诱导视网膜病变小鼠视网膜新生血管的影响

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...

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

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 1 μL of 8.5 g·L^-1 NaCl, 15 mmol·L^-1 DA solution and 602 μmol·L^-1 Quinpirole solution into the vitreous body of right eyes， respectively. The mice in the Spiperone group were injected with 154 μmol·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, the number of endothelial cell nuclei that break through the inner limiting membrane, ratio of neovascularization area, and the relative expressions of VEGF mRNA and protein in the retina of mice in the DA group were significantly decreased (all P<0.05); compared with the DA group, 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 Quinpirole group were significantly declined (all P<0.05).
Conclusion　DA can inhibit the expression of VEGF by activating DRD2 pathway, thereby reducing the production of retinal neovascularization in OIR mice.