[1]陈珊珊,杨中伊,李姝蓉,等.Arresten在氧诱导小鼠视网膜新生血管形成中的抑制作用及机制[J].眼科新进展,2018,38(12):1105-1108.[doi:10.13389/j.cnki.rao.2018.0261]
 CHEN Shan-Shan,YANG Zhong-Yi,LI Shu-Rong,et al.Inhibitory effects and mechanism of Arresten on retinal neovascularization in oxygen-induced retinopathy mice[J].Recent Advances in Ophthalmology,2018,38(12):1105-1108.[doi:10.13389/j.cnki.rao.2018.0261]
点击复制

Arresten在氧诱导小鼠视网膜新生血管形成中的抑制作用及机制/HTML
分享到:

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
38卷
期数:
2018年12期
页码:
1105-1108
栏目:
实验研究
出版日期:
2018-12-05

文章信息/Info

Title:
Inhibitory effects and mechanism of Arresten on retinal neovascularization in oxygen-induced retinopathy mice
作者:
陈珊珊杨中伊李姝蓉刘桥生付书华
330006 江西省南昌市,南昌大学第二附属医院眼科
Author(s):
CHEN Shan-ShanYANG Zhong-YiLI Shu-RongLIU Qiao-ShengFU Shu-Hua
Department of Ophthalmology,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,Jiangxi Province,China
关键词:
Arresten氧诱导视网膜病变视网膜新生血管
Keywords:
arrestenoxygen-induced retinopathyretinal neovascularization
分类号:
R772.2
DOI:
10.13389/j.cnki.rao.2018.0261
文献标志码:
A
摘要:
目的 探讨Arresten在氧诱导小鼠视网膜新生血管形成中的抑制作用及机制。方法 选取48只出生后7 d健康清洁级C57BL/6J幼鼠,随机分为氧诱导视网膜病变(oxygen induced retinopathy,OIR)组、OIR+ Arresten组和常氧组,每组16只。OIR+Arresten组及OIR组幼鼠在体积分数为(75±2)%的高氧环境下饲养5 d,然后转移至正常氧气环境中饲养5 d,其中OIR+Arresten组幼鼠于高氧饲养刚结束时,给予双眼玻璃体内注射Arresten蛋白。常氧组幼鼠则在常规氧气环境中连续饲养10 d。在鼠龄17 d时,各组取6只幼鼠经股静脉注射异硫氰酸葡聚糖溶液处死并摘出眼球,视网膜铺片后观察视网膜的血管形态、计算无灌注区面积。同时对小鼠眼球视网膜行石蜡切片和HE染色,计算侵入玻璃体内血管内皮细胞核的数量。同时,通过细胞培养实验,利用MTT法检测Arresten蛋白对人血管内皮细胞增殖的抑制作用。结果 视网膜铺片结果显示,常氧组、OIR组、OIR+Arresten组视网膜无灌注区相对面积分别为(2.35±1.62)%、(57.28±9.36)%和(20.38±8.69)%,三组间总体比较,差异有统计学意义(F=18.732,P<0.05),且OIR组无灌注区相对面积显著高于OIR+Arresten组,差异有统计学意义(P<0.05)。常氧组小鼠视网膜的内界膜结构仍保持平滑完整,未发现有新生血管侵入玻璃体内。OIR组和OIR+Arresten组每张切片上血管内皮细胞核的数量分别为 (15.18±4.83)个、(7.33±3.88)个,其中OIR+Arresten组侵入玻璃体内新生血管内皮细胞核的数量显著低于OIR组,差异有统计学意义(P<0.05)。Arresten蛋白对人脐静脉内皮细胞增殖的抑制率随着其浓度的升高而增加,但当Arresten蛋白浓度达到1000 μg·L-1时,人脐静脉内皮细胞的增殖抑制率达到顶峰,为(58.00±0.65)%。结论 Arresten蛋白能够抑制氧诱导的小鼠视网膜新生血管形成,通过抑制血管内皮细胞增殖来抑制新生血管形成。
Abstract:
Objective To explore the inhibitory effect and the mechanism of Arresten protein on oxygen-induced retinal neovascularization in mice.Methods At postnatal 7 days (P7),forty-eight C57BL/6J pups were randomly divided into OIR group,OIR +Arresten group and normoxic group,there were 16 pups in each group.The pups in OIR group and OIR+Arresten group were exposed to high oxygen(75±2)%for 5 days.At P12,the pups in OIR+Arresten group were injected intravitreous with Arresten protein,then they were fed under normoxic condition for 5 days.The pups in normoxic group were fed under normoxic condition for 10 days.Six mice in each group were injected with FITC-dextrana via femoral vein at P17,the retinal vascular morphology was observed and the area of noperfusion was calculated.At the same time,paraffin sections and HE staining were performed on the mice retina,the average number of pre-retinal vascular endothelial nuclei were counted.The effect of Arresten protein on the proliferation of human vascular endothelial cells line was detected by MTT assay.Results FITC-dextran labeled retinal whole mounts showed that the relative area of noperfusion area in the normoxic,OIR group and OIR+Arresten were (2.35±1.62)%,(57.28±9.36)% and (20.38±8.69)%,respectively.The OIR group was higher than OIR +Arresten group,there was a statistical significance (P<0.05).The average number of endothelial nuclei in each section of the three groups was 15.18±4.83 and 7.33±3.88,respectively.The number of neovascularized endothelial nuclei in OIR+Arresten group was significantly lower than that in OIR group,and the inhibitory rate of Arresten protein on the proliferation of HUVEC cells were increased with the increase of Arresten protein concentration,but when the concentration of Arresten protein increase to 1000 μg·L-1,the proliferation inhibition rate of HUVEC cells arrived at its peak.Conclusion Arresten can inhibits retinal neovascularization by oxygen-induced via inhibiting the proliferation of vascular endothelial cells in mice.

参考文献/References:

[1] REZZOLA S,BELLERI M,GARIANO G,RIBATTI D,COSTAGLIOLA C,SEMERARO F,et al.In vitro and ex vivo retina angiogenesi assays[J].Angiogenesis,2014,17(3):429-442.
[2] HANAHAN D,FOLKMAN J.Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis[J].Cell,1996,86(3):353-364.
[3] LV Y,ZHANG H F,FU Z D,ZHENG J P.Arresten protein inhibits migration of cervical cancer cells by regulating EMT[J].Chin Reme Clin,2017,17(9):1273-1276.
吕懿,张慧芳,付振东,郑金平.Arresten蛋白通过调控上皮-间质转化抑制宫颈癌细胞的迁移[J].中国药物与临床,2017,17(9):1273-1276.
[4] LI R L,CHEN N,MENG L L,ZHU H.Effect of DNA damage marker γH2AX in the process of oxygen-induced retinal neovascularization[J].Chin J Exp Ophthalmol,2017,35(10):879-884.
李若琳,陈楠,孟丽丽,朱虹.DNA损伤标志物γH2AX在氧诱导视网膜新生血管形成中的作用[J].中华实验眼科杂志,2017,35(10):879-884.
[5] LI S,LI T,LUO Y,YU H,SUN Y,ZHOU H,et al.Retro-orbital injection of FITC-dextran is an effective and economical method for observing mouse retinal vessels[J].Mol Vis,2011,17:3566-3573.
[6] MITITELU M,CHAUDHARY K M,LIEBERMAN R M.An evidence-based meta-analysis of vascular endothelial growth factor inhibition in pediatric retinal diseases:part 1.Retinopathy of prematurity[J].J Pediatr Ophthalmol Strabismus,2012,49(6):332-340.
[7] LI Y,BUSOY J M,ACHIRM B A,ZAMAN B A A,WOON Q T S,TAN G S,et al.A novel model of persistent retinal neovascularization for the development of sustained anti-VEGF therapies[J].Exp Eye Res,2018,174:98-106.
[8] CAMPA C,ALIVERNINI G,BOLLETTA E,PARODI M B,PERRI P.Anti-VEGF therapy for retinal vein occlusions[J].Curr Drug Targets,2016,17 (3):328-336.
[9] BROADHEAD G K,HONG T,CHANG A A.Treating the untreatablc patient:current options for the management of treatment-resistant neovascular age related macular degeneration[J].Acta Ophthalmol,2014,92(8):713-723.
[10] FU S,DONG S,ZHU M,LE Y.VEGF as a trophic factor for Müller glia in hypoxic retinal diseases[J].Adv Exp Med Biol,2018,1074:473-478.
[11] ZHANG Y,HAN Q,RU Y,BO Q,WEI R H.Anti-VEGF treatment for myopic choroid neovaseularization:from molecular characterization to update on clinical application[J].Drug Des Devel Ther,2015,9:3413-3421.
[12] COLORADO P C,TORRE A,KAMPHAUS G,MAESHIMA Y,HOPFER H,TAKAHASHI K,et al.Anti-angiogenic cues from vascular basement membrane collagen[J].Cancer Res,2000,60(9):2520-2526.
[13] ASSADIAN S,El-ASSAAD W,Wang X Q,GANNON P O,BAR-RES V,LATOUR M,et al.p53 inhibits angiogenesis by inducing the production of Arresten[J].Cancer Res,2012,72(5):1270-1279.
[14] AIKIO M,ALAHUHTAl I,NURMENNIEMI S,SUOJANEN J,PALOVUORI R,TEPPO S,et al.Arresten,a collagen-derived angiogenesis inhibitor,suppresses invasion of squamous cell carcinoma[J].PLoS One,2012,7(12):1044-1048.
[15] CHEW L J,PAN H,YU J,TIAN S,HUUANG W Q,ZHANG J Y,et al.A novel secreted splice variant of vascular endothelial cell growth inhibitor[J].FASEB J,2002,16(7):742-744.
[16] ZHANG H F,HUDSON F Z,XU Z M,TRTZ R,ROJAS M,PATEL C,et al.Neurofibromin deficiency induces endothelial cell proliferation and retinal neovascularization[J].Invest Ophthalmol Vis Sci,2018,59(6):2520-2528.

相似文献/References:

[1]田丽丽 任兵 高晓唯 罗英 蔡岩 周琨 杜安杰. 玻璃体内注射索拉非尼对大鼠氧诱导视网膜病变模型新生血管的作用[J].眼科新进展,2014,34(2):140.
[2]万志荔,赖史胜.高迁移率族B1(HMGB-1)蛋白在鼠视网膜新生血管形成中的调控作用[J].眼科新进展,2014,34(12):1128.[doi:10.13389/j.cnki.rao.2014.0313]
 WAN Zhi-Li,LAI Shi-Sheng.Mediation effects of high mobility group B1 protein on retinal neovascularization in mice[J].Recent Advances in Ophthalmology,2014,34(12):1128.[doi:10.13389/j.cnki.rao.2014.0313]
[3]高翔,王雨生. 巨噬细胞在小鼠氧诱导视网膜新生血管形成中的作用[J].眼科新进展,2015,35(3):201.[doi:10.13389/j.cnki.rao.2015.0055]
 GAO Xiang,WANG Yu-Sheng. Role of macrophages in oxygen-induced retinal neovas-cularization in mice[J].Recent Advances in Ophthalmology,2015,35(12):201.[doi:10.13389/j.cnki.rao.2015.0055]
[4]李晓琴,张自峰,王雨生,等. 脂多糖诱导炎症对大鼠氧诱导视网膜病变的影响[J].眼科新进展,2015,35(4):301.[doi:10.13389/j.cnki.rao.2015.0081]
 LI Xiao-Qin,ZHANG Zi-Feng,WANG Yu-Sheng,et al. Effects of LPS-induced inflammation on oxygen-induced retinopathy in rats[J].Recent Advances in Ophthalmology,2015,35(12):301.[doi:10.13389/j.cnki.rao.2015.0081]
[5]张景尚,安莹,王进达,等.毛花甙丙抑制氧诱导乳鼠视网膜新生血管的实验研究[J].眼科新进展,2016,36(7):612.[doi:10.13389/j.cnki.rao.2016.0162]
 ZHANG Jing-Shang,AN Ying,WANG Jin-Da,et al.Digilanid C inhibiting retinal neovascularization in oxygen induced retinopathy of mice[J].Recent Advances in Ophthalmology,2016,36(12):612.[doi:10.13389/j.cnki.rao.2016.0162]
[6]底煜,陈晓隆.磷脂酰肌醇-3-激酶/丝氨酸-苏氨酸激酶抑制剂LY294002对小鼠视网膜新生血管形成的抑制作用[J].眼科新进展,2018,38(3):210.[doi:10.13389/j.cnki.rao.2018.0048]
 DI Yu,CHEN Xiao-Long.Inhibitory effects of PI3K/AKT inhibitor LY294002 on retinal neovascularization in mice[J].Recent Advances in Ophthalmology,2018,38(12):210.[doi:10.13389/j.cnki.rao.2018.0048]
[7]薛盛丁,陈辉,刘爽,等.甲酰肽受体Fpr2在氧诱导视网膜病变小鼠新生血管形成中的作用及相关机制研究[J].眼科新进展,2021,41(6):522.[doi:10.13389/j.cnki.rao.2021.0109]
 XUE Shengding,CHEN Hui,LIU Shuang,et al.Role of formyl peptide receptor Fpr2 on neovascularization in rats with oxygen-induced retinopathy and its mechanism[J].Recent Advances in Ophthalmology,2021,41(12):522.[doi:10.13389/j.cnki.rao.2021.0109]

备注/Memo

备注/Memo:
国家自然科学基金资助(编号:81660164);江西省自然科学基金重点项目(编号:20171ACB20036);江西省自然科学基金(编号:2015BAB205026、2015BBG70171);南昌大学第二附属医院博士启动基金(编号:B1728#)
更新日期/Last Update: 2018-12-04