雷珠单抗对脉络膜新生血管模型大鼠视网膜氧化应激的抑制作用及其机制  

Inhibitory effect of ranibizumab on retinal oxidative stress in a rat model of choroidal neovascularization and its mechanism

作　　者：杨延振[1] 庄宪丽[1] 李树杰[1] 张莹[1] 杨家干[1] 李路路[1] Yang Yanzhen;Zhuang Xianli;Li Shujie;Zhang Ying;Yang Jiagan;Li Lulu(Department of Ophthalmology,Tengzhou Central People's Hospital,Tengzhou 277500,China)

机构地区：[1]滕州市中心人民医院眼科,滕州277500

出　　处：《中华实验眼科杂志》2023年第1期22-28,共7页Chinese Journal Of Experimental Ophthalmology

基　　金：山东省医药卫生科技发展计划项目(2018WSA05655)。

摘　　要：目的研究雷珠单抗对脉络膜新生血管(CNV)模型大鼠视网膜氧化应激的作用及其机制。方法选取10周龄SPF级雄性SD大鼠60只,按照随机数字表法随机分为正常对照组、模型对照组、雷珠单抗组、转录因子核因子E2相关因子2(Nrf2)抑制剂(ML385)组、雷珠单抗+ML385组,每组12只。除正常对照组外,其余各组以氪激光诱导CNV模型。雷珠单抗组、ML385组和雷珠单抗+ML385组分别玻璃体腔内注射1μl雷珠单抗、ML385、雷珠单抗+ML385,模型对照组、正常对照组分别给予玻璃体腔内注射等体积生理盐水。脉络膜铺片法检测CNV面积;苏木精-伊红染色观察视网膜病理学变化;实时荧光定量PCR及Western blot检测视网膜组织中Nrf2、超氧化物歧化酶(SOD)、醌氧化还原酶(NQO1)mRNA及蛋白表达水平。结果模型对照组、ML385组和雷珠单抗+ML385组CNV面积分别为(23.01±1.52)×10^(3)、(30.23±2.01)×10^(3)和(18.56±1.85)×10^(3)μm^(2),明显高于雷珠单抗组的(12.35±1.22)×10^(3)μm^(2),雷珠单抗+ML385组CNV面积小于模型对照组和ML385组,ML385组CNV面积大于模型对照组,差异均有统计学意义(均P<0.001)。苏木精-伊红染色结果显示,雷珠单抗组RPE-脉络膜-巩膜复合体结构损害程度较模型对照组轻;雷珠单抗+ML385组RPE-脉络膜-巩膜复合体结构损害程度较雷珠单抗组重,但较模型对照组轻;ML385组RPE-脉络膜-巩膜复合体结构损害较模型对照组严重。雷珠单抗组Nrf2、SOD和NQO1 mRNA及蛋白相对表达量均低于正常对照组,但高于模型对照组、ML385组和雷珠单抗+ML385组,且雷珠单抗+ML385组Nrf2、SOD和NQO1 mRNA及蛋白相对表达量高于模型对照组和ML385组,差异均有统计学意义(均P<0.05)。结论雷珠单抗可抑制氪激光诱导的CNV生长,减轻RPE氧化应激损伤,其机制与Nrf2/ARE通路的激活有关。Objective To study the effect of ranibizumab on retinal oxidative stress in a rat model of choroidal neovascularization(CNV)and its mechanism.Methods Sixty SPF male SD rats aged 10 weeks were randomly divided into normal control group,model control group,ranibizumab group,nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor(ML385)group,ranibizumab+ML385 group,with 12 rats in each group according to a random number table.Except for the normal control group,the CNV model was established in the other four groups via krypton laser induction.According to grouping,the ranibizumab group,ML385 group and ranibizumab+ML385 group were intravitreally injected with 1μl of ranibizumab,ML385 and ranibizumab+ML385,respectively.Model control group and normal control group received an intravitreal injection of normal saline of equal volume.The CNV area was measured through choroidal wholemounts.Pathological change of the retina was observed by hematoxylin and eosin staining.Expressions of Nrf2,superoxide dismutase(SOD)and quinone oxidoreductase 1(NQO1)were detected using Western blot and real-time PCR.The use and care of animals complied with laboratory animal welfare guidelines.The study protocol was approved by the Laboratory Animal Welfare and Ethics Committee of Tengzhou Central People's Hospital(No.JN.No20210214S1200430[121]).Results CNV areas of the model control group,ML385 group and ranibizumab+ML385 group were(23.01±1.52)×10^(3),(30.23±2.01)×10^(3)and(18.56±1.85)×10^(3)μm^(2),respectively,which were significantly higher than(12.35±1.22)×10^(3)μm^(2)of ranibizumab group(all at P<0.001).The CNV area of ranibizumab+ML385 group was smaller than that of model control group and ML385 group,and the CNV area of ML385 group was larger than that of model control group,showing statistically significant differences(all at P<0.001).Hematoxylin and eosin staining showed that the structural damage of the retinal pigment epithelium-choroid-sclera complex was slighter in ranibizumab group than model control group,severer

关 键 词：雷珠单抗 黄斑变性 视网膜 氧化应激 

分 类 号：R773.4[医药卫生—眼科] R-332[医药卫生—临床医学]