树枝状大分子N-乙酰半胱氨酸(D-NAC)对氧诱导视网膜病变小鼠视网膜血管重建的影响及其作用机制  

Effects of Dendrimer-N-acetylcysteine on retinal revascularization in oxygen-induced retinopathy mice and related mechanisms

作　　者：杨静 胡宝琪 刘茹佳 齐赟 YANG Jing;HU Baoqi;LIU Rujia;QI Yun(Department of Health Medicine,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,China;Department of Ophthalmology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,China)

机构地区：[1]西安交通大学第一附属医院健康医学科,陕西省西安市710061 [2]西安交通大学第一附属医院眼科,陕西省西安市710061

出　　处：《眼科新进展》2025年第4期276-280,共5页Recent Advances in Ophthalmology

基　　金：陕西省自然科学基础研究计划(编号:2022JQ-937,2024JC-YBMS-690)。

摘　　要：目的探讨树枝状大分子N-乙酰半胱氨酸(D-NAC)对氧诱导视网膜病变(OIR)小鼠视网膜血管重建的影响及其作用机制。方法取7 d龄健康级C57BL/6J小鼠14只,制造OIR小鼠模型后将小鼠按眼别分为两组:对照组和实验组。对照组小鼠左眼玻璃体内注射浓度为1 g·L^(-1)的树枝状大分子Dendrimer 1μL;实验组小鼠右眼玻璃体内注射浓度为1 g·L^(-1)的D-NAC 1μL。采用视网膜铺片荧光染色法和Photoshop软件计算各组小鼠血管闭塞区面积和病理性新生血管面积,qRT-PCR检测小鼠视网膜炎症因子mRNA表达,ELISA检测小鼠视网膜肿瘤坏死因子α(TNF-α)蛋白含量。采用SPSS18.0统计软件对数据进行统计学分析。结果在出生后第17天,实验组小鼠视网膜血管闭塞区面积[(13.55±3.42)mm^(2)]小于对照组[(21.92±3.13)mm^(2)],面积减少38.18%,差异有统计学意义(t=17.76,P<0.01);实验组小鼠视网膜病理性新生血管面积[(7.24±2.11)mm^(2)]低于对照组[(10.12±2.74)mm^(2)],差异有统计学意义(t=2.91,P<0.05)。出生后第16天,实验组小鼠视网膜炎症因子TNF-α、IL-1β、IL-6、ICAM-1、CCL-7的mRNA相对表达量均低于对照组,差异均有统计学意义(均为P<0.05)。出生后第16天,实验组小鼠视网膜GFAP(星形胶质细胞活化标志物)和IBA-1(小胶质细胞活化标志物)的mRNA相对表达量均低于对照组,差异均有统计学意义(均为P<0.05)。ELISA检测结果显示,出生后第16天,实验组小鼠视网膜TNF-α含量[(16.40±5.58)ng·g^(-1)]低于对照组[(22.01±5.82)ng·g^(-1)],含量降低25.49%,差异有统计学意义(t=7.81,P=0.002)。结论玻璃体内注射D-NAC可能通过降低视网膜炎症因子水平、抑制星形胶质细胞和小胶质细胞的活化,从而促进OIR小鼠视网膜血管重建。Objective To explore the effects of Dendrimer-N-acetylcysteine(D-NAC)on retinal revascularization in oxygen-induced retinopathy(OIR)mice and related mechanisms.Methods Fourteen healthy C57BL/6J mice aged 7 days were used to establish an OIR mouse model.The mice were then divided into a control group and an experimental group.The control group was injected intravitreally with 1μL of Dendrimer at a concentration of 1 g·L^(-1)into the left eye.The experimental group was injected intravitreally with 1μL of D-NAC at a concentration of 1 g·L^(-1)into the right eye.Fluorescence staining of retina flat-mounting and Photoshop software were used to calculate the areas of vaso-obliteration and pathological neovascularization in each group of mice.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of inflammatory factors in the mouse retina.Enzyme-linked immunosorbent assay(ELISA)was used to detect the protein expression of tumor necrosis factor-α(TNF-α)in the mouse retina.SPSS18.0 software was used for statistical analysis of data.Results The area of vaso-obliteration in the experimental group[(13.55±3.42)mm^(2)]was 38.18%smaller than that in the control group on the 17th day after birth[(21.92±3.13)mm^(2)](t=17.76,P<0.01).The area of pathological neovascularization in the experimental group[(7.24±2.11)mm^(2)]was significantly smaller than that in the control group[(10.12±2.74)mm^(2)](t=2.91,P<0.05).The relative mRNA expression levels of TNF-α,interleukin-1β(IL-1β),interleukin-6(IL-6),intercellular adhesion molecule 1(ICAM-1)and c-c motif chemokine ligand-7(CCL-7)in the mouse retina of the experimental group were significantly lower than those of the control group on the 16th day after birth(all P<0.05).The relative mRNA expression levels of the astrocyte activation marker,glial fibrillary acidic proteins(GFAP),and the microglial activation marker,ionized calcium binding adaptor molecule 1(IBA-1)in the mouse retina of the experimental group were si

关 键 词：树枝状大分子 N-乙酰半胱氨酸 氧诱导视网膜病变 血管重建 炎症 

分 类 号：R774.1[医药卫生—眼科]