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  

Effects of intravitreal injection of sorafenib on neovascularization in oxygen-induced retinopathy of rat

作　　者：田丽丽[1,2] 任兵[2] 高晓唯[2] 罗英[2] 蔡岩[2] 周琨[1,2] 杜安杰 

机构地区：[1]石河子大学医学院,新疆维吾尔自治区石河子市830002 [2]解放军第474医院全军眼科中心,新疆维吾尔自治区乌鲁木齐市830013 [3]山西省运城市中心医院眼科,044000

出　　处：《眼科新进展》2014年第2期140-143,共4页Recent Advances in Ophthalmology

摘　　要：目的探讨玻璃体内注射索拉非尼对氧诱导视网膜病变(oxygen-induced retinopathy,OIR)大鼠模型视网膜新生血管的作用。方法 7 d龄SD乳鼠144只,随机分为6组:A组:对照组;B组:ROP组;C组:ROP溶媒对照组;D组:ROP+5μg索拉非尼组;E组:ROP+20μg索拉非尼组;F组:ROP+80μg索拉非尼组。除A组在正常氧环境下饲养外,其余各组乳鼠均建立OIR模型。乳鼠于生后第12天出氧箱后给予玻璃体内注射DMSO及相应剂量的索拉非尼,于生后第17天处死,做视网膜铺片,并于激光共聚焦显微镜下观察视网膜血管形态并在高倍视野下计数血管分支点数目;组织切片HE染色观察视网膜组织形态并计数突破内界膜的血管内皮细胞核数。结果视网膜铺片显示,B组和C组视网膜血管迂曲扩张并形成大量新生血管,经索拉非尼治疗后,视网膜新生血管大幅度减少,且呈剂量依赖性。A组、B组、C组、D组、E组、F组血管分支点数目分别为(16.50±3.90)个、(37.44±6.47)个、(37.08±5.10)个、(30.80±6.85)个、(26.08±5.08)个、(19.83±3.51)个;除B组与C组差异无统计学意义外,其余各组间差异均有统计学意义(均为P<0.05)。HE染色显示,B组和C组有大量突破内界膜的血管内皮细胞核,经索拉非尼治疗后,突破内界膜的血管内皮细胞核明显减少,且呈剂量依赖性。A组、B组、C组、D组、E组、F组突破视网膜内界膜的血管内皮细胞核数分别为(0.22±0.42)个、(35.66±4.70)个、(35.30±4.54)个、(27.30±4.28)个、(21.41±3.53)个、(7.41±2.87)个;除B组与C组间差异无统计学意义外,其余各组间差异均有统计学意义(均为P<0.05)。结论索拉非尼能够有效抑制大鼠OIR模型视网膜新生血管的生成,且抑制效果呈剂量依赖性。Objective To investigate the effects of intravitreal injection of sor- afenib on neovascularization model of oxygen-induced retinopathy （OIR） of rat. Meth- ods Seven-day-old Sprague-Dawley rats （ 144 cases）were randomly divided into con- trolled group （group A） ,ROP group （group B）,vehicle-treated ROP group （group C）, 5 μg sorafenib-treated ROP group （group D）, 20 μg sorafenib-treated ROP group （group E）and 80 μg sorafenib-treated ROP group （group A）. Group A received normal partial oxygen pressure, and group B, C, D, E and F were established the OIR model. Then,at postnatal 12 days,the rats were returned to normal oxygen till P17. The rats in groups D,E and F were received intravitreal injections of sorafenib （5 μg,20 μg and 80 pLg,respectively） at postnatal 12 days. The rats in groups C were received intravitreal in- jections of DMSO. Then the retinas were whole-mounted and imaged with a confocal microscope. The vascular branching points were counted to quantify neovascularization in high magnification at postnatal 17 days. Cross-sections of the retina were stained with HE. The nuclei of new vessels breaking through the internal limiting membrane were counted to quantify the proliferative neovascular response. Results Retinal flat mounts shows that the retinal vessel in group B and C turned into tortuosity. Moreover, great deals of neovascularization were observed. Sorafenib-treated rats had significantly less neovascularization as compared with vehicle-treated and control rats in a dose de- pendent manner. The number of vascular branching points in group A, B, C, D, E and F were 15.50 ± 3.90,37.44 ± 5.47,37.08 ± 5.10,30. 80 ± 5.85,25.08± 5.08 and 19.83 ± 3.51 ,respectively, there were statistical differences between each group except for group B and group C （ all P 〈 0.05 ）. HE staining showed that there were large numbers of retinal new vessel nuclei in group B and C. After treated with sorafenib, the number reduced significantly with a dose dependent manne

关 键 词：索拉非尼 氧诱导视网膜病变 新生血管 酪氨酸激酶抑制剂 

分 类 号：R774.1[医药卫生—眼科]