[1]张凤一,高洪莲,邱宇,等.多巴胺对氧诱导视网膜病变小鼠视网膜新生血管的影响[J].眼科新进展,2023,43(1):025-29.[doi:10.13389/j.cnki.rao.2023.0005]
 ZHANG Fengyi,GAO Honglian,QIU Yu,et al.Effect of dopamine on retinal neovascularization in oxygen-induced retinopathy mice[J].Recent Advances in Ophthalmology,2023,43(1):025-29.[doi:10.13389/j.cnki.rao.2023.0005]
点击复制

多巴胺对氧诱导视网膜病变小鼠视网膜新生血管的影响/HTML
分享到:

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
43卷
期数:
2023年1期
页码:
025-29
栏目:
实验研究
出版日期:
2023-01-05

文章信息/Info

Title:
Effect of dopamine on retinal neovascularization in oxygen-induced retinopathy mice
作者:
张凤一高洪莲邱宇崔钰莹李童王亚彤张磊
256600 山东省滨州市,滨州医学院附属医院(第一临床医学院)眼科(张凤一,邱宇,崔钰莹,李童,王亚彤,张磊);256600 山东省滨州市,滨州医学院附属医院(第一临床医学院)医学研究中心(高洪莲)
Author(s):
ZHANG Fengyi1GAO Honglian2QIU Yu1CUI Yuying1LI Tong1WANG Yatong1ZHANG Lei1
1.Department of Ophthalmology,the Affiliated Hospital of Binzhou Medical University,Binzhou 256600,Shandong Province,China
2.Medical Research Center,the Affiliated Hospital of Binzhou Medical University,Binzhou 256600,Shandong Province,China
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
Keywords:
vascular endothelial growth factor retinal neovascularization dopamine oxygen-induced retinopathy model mice
分类号:
R774.1
DOI:
10.13389/j.cnki.rao.2023.0005
文献标志码:
A
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、602 μmol·L-1的Quinpirole溶液,Spiperone组小鼠右眼玻璃体内依次注射154 μmol·L-1的Spiperone溶液和15 mmol·L-1的DA溶液各1 μL。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。
Abstract:
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.

参考文献/References:

[1] RIVERA J C,HOLM M,AUSTENG D,MORKEN T S,ZHOU T E,BEAUDRY-RICHARD A,et al.Retinopathy of prematurity:inflammation,choroidal degeneration,and novel promising therapeutic strategies[J].J Neuroinflammation,2017,14(1):165.
[2] TRAN K D,CERNICHIARO-ESPINOSA L A,BERROCAL A M.Management of retinopathy of prematurity:use of anti-VEGF therapy[J].Asia Pac J Ophthalmol (Phila),2018,7(1):56-62.
[3] 海峡两岸医药卫生交流协会眼科专业委员会小儿视网膜学组,中华医学会眼科学分会眼底病学组.早产儿视网膜病变玻璃体腔注射抗血管内皮生长因子药物治疗的专家共识[J].中华眼底病杂志,2021,37(11):836-840.
Pediatric Retinology Group,Ophthalmology Committee,Cross-strait Medical and Health Exchange Association;Ophthalmology Group,Ophthalmology Branch,Chinese Medical Association.Expert consensus on intravitreal injection of anti-vascular endothelial growth factor for retinopathy of prematurity[J].Chin J Ocul Fundus Dis,2021,37(11):836-840.
[4] 邱宇,高洪莲,于睿,李欣蒙,崔钰莹,张磊.抗血管内皮生长因子玻璃体内注射对形觉剥夺性近视豚鼠视网膜中多巴胺水平的影响[J].眼科新进展,2022,42(2):113-117.
QIU Y,GAO H L,YU R,LI X M,CUI Y Y,ZHANG L.Effects of intravitreal injection of vascular endothelial growth factor on dopamine levels in the retina of guinea pigs with form-deprived myopia[J].Rec Adv Ophthalmol,2022,42(2):113-117.
[5] MCCARTHY C S,MEGAW P,DEVADAS M,MORGAN I G.Dopaminergic agents affect the ability of brief periods of normal vision to prevent form-deprivation myopia[J].Exp Eye Res,2007,84(1):100-107.
[6] TOLSTANOVA G,DENG X,AHLUWALIA A,PAUNOVIC B,PRYSIAZHNIUK A,OSTAPCHENKO L,et al.Role of dopamine and D2 dopamine receptor in the pathogenesis of inflammatory bowel disease[J].Dig Dis Sci,2015,60(10):2963-2975.
[7] BASU S,SARKAR C,CHAKROBORTY D,NAGY J,MITRA R B,DASGUPTA P S,et al.Ablation of peripheral dopaminergic nerves stimulates malignant tumor growth by inducing vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis[J].Cancer Res,2004,64(16):5551-5555.
[8] CHAKROBORTY D,SARKAR C,MITRA R B,BANERJEE S,DASGUPTA P S,BASU S.Depleted dopamine in gastric cancer tissues:dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis[J].Clin Cancer Res,2004,10(13):4349-4356.
[9] SHOME S,RANA T,GANGULY S,BASU B,CHAKI CHOUDHURY S,SARKAR C,et al.Dopamine regulates angiogenesis in normal dermal wound tissues[J].PLoS One,2011,6(9):e25215.
[10] SMITH L E,WESOLOWSKI E,MCLELLAN A,KOSTYK S K,D’AMATO R,SULLIVAN R,et al.Oxygen-induced retinopathy in the mouse[J].Invest Ophthalmol Vis Sci,1994,35(1):101-111.
[11] LYU J,ZHANG Q,CHEN C L,XU Y,JI X D,LI J K,et al.Recurrence of retinopathy of prematurity after intravitreal ranibizumab monotherapy:timing and risk factors[J].Invest Ophthalmol Vis Sci,2017,58(3):1719-1725.
[12] RIVERA J C,DABOUZ R,NOUEIHED B,OMRI S,TAHIRI H,CHEMTOB S.Ischemic retinopathies:oxidative stress and inflammation[J].Oxid Med Cell Longev,2017,2017:3940241.
[13] WARD A H,SIEGWART J T,FROST M R,NORTON T T.Intravitreally-administered dopamine D2-like (and D4),but not D1-like,receptor agonists reduce form-deprivation myopia in tree shrews[J].Vis Neurosci,2017,34:E003.
[14] OSINGA T E,LINKS T P,DULLAART R P F,PACAK K,VAN DER HORST-SCHRIVERS A N A,KERSTENS M N,et al.Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma[J].Faseb J,2017,31(6):2226-2240.
[15] SARKAR C,CHAKROBORTY D,DASGUPTA P S,BASU S.Dopamine is a safe antiangiogenic drug which can also prevent 5-fluorouracil induced neutropenia[J].Int J Cancer,2015,137(3):744-749.
[16] CHAKROBORTY D,GOSWAMI S,BASU S,SARKAR C.Catecholamines in the regulation of angiogenesis in cutaneous wound healing[J].Faseb J,2020,34(11):14093-14102.
[17] SARKAR C,CHAKROBORTY D,MITRA R B,BANERJEE S,DASGUPTA P S,BASU S.Dopamine in vivo inhibits VEGF-induced phosphorylation of VEGFR-2,MAPK,and focal adhesion kinase in endothelial cells[J].Am J Physiol Heart Circ Physiol,2004,287(4):H1554-1560.
[18] SINHA S,VOHRA P K,BHATTACHARYA R,DUTTA S,SINHA S,MUKHOPADHYAY D.Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2[J].J Cell Sci,2009,122(Pt 18):3385-3392.
[19] BASU S,NAGY J A,PAL S,VASILE E,ECKELHOEFER I A,BLISS V S,et al.The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor[J].Nat Med,2001,7(5):569-574.
[20] HOEPPNER L H,WANG Y,SHARMA A,JAVEED N,VAN KEULEN V P,WANG E,et al.Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells[J].Mol Oncol,2015,9(1):270-281.
[21] FAN S F,YAZULLA S.Suppression of voltage-dependent K+ currents in retinal bipolar cells by ascorbate[J].Vis Neurosci,1999,16(1):141-148.
[22] PRAN BABU S P S,WHITE D,CORSON T W.Ferrochelatase regulates retinal neovascularization[J].Faseb J,2020,34(9):12419-12435.
[23] THOMSON K,KAROUTA C,ASHBY R.Form-deprivation and lens-induced myopia are similarly affected by pharmacological manipulation of the dopaminergic system in chicks[J].Invest Ophthalmol Vis Sci,2020,61(12):4.
[24] CRISTINA C,DAZ-TORGA G,BALDI A,GNGORA A,RUBINSTEIN M,LOW M J,et al.Increased pituitary vascular endothelial growth factor-a in dopaminergic D2 receptor knockout female mice[J].Endocrinology,2005,146(7):2952-2962.
[25] WITKOVSKY P.Dopamine and retinal function[J].Doc Ophthalmol,2004,108(1):17-40.

相似文献/References:

[1]程文武 江萍 席祖莲 张汉武 訾世莉 聂军 董彩虹.蛹虫草提取物抑制大鼠角膜新生血管的实验研究[J].眼科新进展,2012,32(5):000.
[2]于静 张明昌.苦参碱对大鼠角膜新生血管的抑制作用[J].眼科新进展,2012,32(6):000.
[3]吴正正 严京 接传红 高健生 陈皆春 宋剑涛.密蒙花方对缺氧状态下脐静脉血管内皮细胞 VEGF-VEGFR 信号转导通路的影响[J].眼科新进展,2012,32(7):000.
[4]庞霞 曲蕴慧 马跃伟 张效房 董敬民 高冬玲.去整合素金属蛋白酶9和血管内皮生长因子蛋白在眼部恶性黑色素瘤中的表达[J].眼科新进展,2012,32(7):000.
[5]李艳 李筱荣 袁佳琴 潘斌.糖尿病大鼠视网膜中VEGF、PEDF的表达与血-视网膜屏障损伤[J].眼科新进展,2013,33(1):000.
[6]许琴 黄亮 林素香 郑水华 肖煜晨 王雅丽.激光诱导小鼠脉络膜新生血管中膜攻击物与血管生长因子的表达[J].眼科新进展,2013,33(8):000.
[7]李小璐 马雅玲.糖尿病视网膜病变大鼠视网膜VEGF和PEDF的动态表达[J].眼科新进展,2013,33(9):000.
[8]曾莉 常以力 邵毅.血管内皮生长因子反义寡脱氧核苷酸联合血管生成素-1对糖尿病视网膜病变大鼠视网膜血管渗漏及新生血管生成的影响[J].眼科新进展,2012,32(10):000.
[9]兰兰 惠延年 曾光伟.血管生成素-1对糖尿病大鼠视网膜微血管病变、基质金属蛋白酶和血管内皮生长因子的抑制作用[J].眼科新进展,2012,32(10):000.
[10]谢明捷 吕红彬 何跃 赵春会.炎症因子与糖尿病视网膜病变相关性研究进展[J].眼科新进展,2012,32(10):000.
[11]迟源 王海林 谢晚晴 才文卓 才丽平.MicroRNA调节视网膜新生血管研究进展[J].眼科新进展,2013,33(2):000.
[12]耿金 陈蕾 柳力敏 刘宁宁 刘磊.β-榄香烯抑制氧诱导小鼠视网膜新生血管形成的实验研究[J].眼科新进展,2013,33(3):000.
[13]贺玲 郑晓龙 张杰 张善峰 余晓红 宋海云.熊果酸对氧诱导小鼠视网膜病变的保护作用[J].眼科新进展,2013,33(10):000.
[14]刘昳,袁进.核转录因子-κB在氧诱导血管增殖性视网膜病变小鼠中的表达[J].眼科新进展,2014,34(12):1101.[doi:10.13389/j.cnki.rao.2014.0306]
 LIU Yi,YUAN Jin.Expression of nuclear factor-kappa B in mice with oxygen-induced proliferative retinopathy[J].Recent Advances in Ophthalmology,2014,34(1):1101.[doi:10.13389/j.cnki.rao.2014.0306]
[15]底煜,张轶欧,王爱媛,等.Cyr61和VEGF在高氧诱导鼠视网膜新生血管中的表达[J].眼科新进展,2015,35(1):015.[doi:10.13389/j.cnki.rao.2015.0004]
 DI Yu,ZHANG Yi-Ou,WANG Ai-Yuan,et al.Expression of Cyr61 and VEGF in hyperxia-induced retinal neovascularization of mice[J].Recent Advances in Ophthalmology,2015,35(1):015.[doi:10.13389/j.cnki.rao.2015.0004]
[16]张翀,陈蕾,李婷婷.血管生成素-1对小鼠视网膜新生血管和血管内皮生长因子的抑制作用[J].眼科新进展,2015,35(1):031.[doi:10.13389/j.cnki.rao.2015.0009]
 ZHANG Chong,CHEN Lei,LI Ting-Ting.Inhibitory effects of angiopoietin-1 on retinal neovas-cularization and VEGF of mice[J].Recent Advances in Ophthalmology,2015,35(1):031.[doi:10.13389/j.cnki.rao.2015.0009]
[17]张飞宇,黄敏丽.糖尿病视网膜血管病变中未折叠蛋白反应:蛋白质折叠的意义和治疗潜力[J].眼科新进展,2018,38(12):1196.[doi:10.13389/j.cnki.rao.2018.0282]
 ZHANG Fei-Yu,HUANG Min-Li.Unfolded protein response in diabetic retinopathy:significance and therapeutic potential of protein folding[J].Recent Advances in Ophthalmology,2018,38(1):1196.[doi:10.13389/j.cnki.rao.2018.0282]
[18]李蓉,姚杨,杜军辉,等.自噬在高糖条件下视网膜色素上皮细胞表达血管内皮生长因子促进RF/6A细胞血管生成中的作用[J].眼科新进展,2019,39(8):714.[doi:10.13389/j.cnki.rao.2019.0163]
 LI Rong,YAO Yang,DU Jun-Hui,et al.Autophagy promotes angiogenesis of RF/6A cells following upregulating the expression of vascular endothelial growth factor in retinal pigment epithelial cells under high glucose conditions[J].Recent Advances in Ophthalmology,2019,39(1):714.[doi:10.13389/j.cnki.rao.2019.0163]
[19]王月,王雪,底煜.长链非编码RNA在早产儿视网膜病变中的作用研究进展[J].眼科新进展,2020,40(11):1097.[doi:10.13389/j.cnki.rao.2020.0244]
 WANG Yue,WANG Xue,DI Yu.Research progress of long non-coding RNA in retinopathy of prematurity[J].Recent Advances in Ophthalmology,2020,40(1):1097.[doi:10.13389/j.cnki.rao.2020.0244]

更新日期/Last Update: 2023-01-05