熊果酸对氧诱导小鼠视网膜病变的保护作用  

Protection of ursolic acid to oxygen-induced retinopathy in rats

作　　者：贺玲 郑晓龙 张杰 张善峰[2] 余晓红 宋海云 

机构地区：[1]解放军第371医院眼科,河南省新乡市453000 [2]郑州大学基础医学院,河南省郑州市450000

出　　处：《眼科新进展》2013年第10期918-921,926,共5页Recent Advances in Ophthalmology

基　　金：河南省新乡市重点科技攻关计划基金资助(编号:ZG12013)~~

摘　　要：目的观察熊果酸(ursolic acid,UA)玻璃体内注射对小鼠氧诱导视网膜病变的保护作用。方法将7 d龄清洁级C57BL/6J小鼠120只,用随机数字表法随机分为6组:空白对照组、模型对照组(PBS液)、阳性对照组(曲安奈德对照)和低剂量、中剂量、高剂量UA干预组,每组20只小鼠(均取右眼为实验对象)。空白对照组小鼠在空气中喂养,其他各组小鼠制备氧诱导视网膜病变模型。造模成功后,各组立即给予相应的药物治疗:模型对照组小鼠玻璃体内注射PBS液3μL,低剂量、中剂量、高剂量UA干预组小鼠玻璃体内分别注射1.5μg·L-1、3.0μg·L-1、6.0μg·L-1UA各3μL,阳性对照组小鼠玻璃体内注射曲安奈德(1 mL∶40 mg)3μL。17 d龄时过量麻醉处死小鼠,摘除眼球制备视网膜组织切片,HE染色,计数突破视网膜内界膜的新生血管内皮细胞核数,利用免疫组织化学法检测视网膜组织中VEGF、COX-2及MMP-2的阳性表达。结果模型对照组小鼠每张切片突破视网膜内界膜的新生血管内皮细胞核数为(18.65±3.24)个,明显高于空白对照组的(0.78±0.11)个,高剂量、中剂量UA干预组分别为(7.93±1.09)个和(13.32±1.87)个,均明显低于模型对照组,差异均有统计学意义(均为P<0.05)。不同组别视网膜组织中COX-2、VEGF和MMP-2蛋白的积分光密度值比较:模型对照组明显高于空白对照组,高剂量、中剂量UA干预组均明显低于模型对照组,差异均有统计学意义(均为P<0.05)。视网膜HE染色结果显示,空白对照组内界膜结构均一,血管内皮细胞排列整齐,偶见血管内皮细胞突破内界膜;模型对照组可见大量血管内皮细胞团突破内界膜,形成新生血管腔;低剂量UA干预组与模型对照组结果基本相似;高剂量UA干预组与阳性对照组结果接近,可见少量血管内皮细胞核突破内界膜,内界膜结构较均一,新生血管腔少见。结论 UA通过降低视网膜组织中的VEGF、COX-2及MMP-2的表�Objective To observe the protection of intravitreal injection of ursol-ic acid （UA） to oxygen-induced retinopathy in rats. Methods One hundred and twenty C57BL/6J rats of pathogen-free aged 7 days were randomly and evenly divided into 6 groups：blank control group, model control group （PBS solution）, positive control group （triamcinolone acetonide ）, UA intervention group （low, middle and high dosa- ges）. All the right eyes were the experimental objects. The rats in blank control group were fed in the air, and neovascularization model was established by the rats in other groups. After the model establishment, rats in each group were given the corresponding drug at once：rats in model control group were given intravitreal injection of 3 μL PBS solution;rats in UA intervention group （low, middle and high dosages ） were given in- travitreal injection of 3 μL UA of 1.5 μg · L- 1,3.0 μg · L- 1, and 6.0 μg · L -1, respec- tively;the positive control group was given intravitreal injection of 3 ~L triamcinolone acetonide（ 1 mL ： 40 mg）. Rats aged 17 days were killed through excessive anesthesia and the eyes were removed to prepare retinal tissue sections. Endotheliocyte nuclei of new vessels beyond the inner limiting membrane in sections were counted with HE stai- ning, and the positive expression of VEGF, COX-2 and MMP-2 in retinal tissues was de- tected by immunohistochemistry. Results The number of endotheliocyte nuclei of new vessels beyond the inner limiting membrane in each section of model control group was 18.65 ± 3.24, significantly higher than that of blank control group （ 0.78 ± 0. 11 ） ; UA intervention group of high and middle dosages were 7.93 ± 1.09 and 13.32 ± 1.87, respectively ,both significantly lower than that of model control group. All the differ- ences were of statistical significance （ all P 〈 0.05 ）. Integrated optical density compari- son of COX-2, VEGF and MMP-2 in retinal tissues of different groups： model control groups markedly higher than

关 键 词：视网膜新生血管 熊果酸 基质金属蛋白酶-2 血管内皮生长因子 环氧化酶-2 

分 类 号：R587.102[医药卫生—内分泌]