Tian Li-Li, Ren Bing, Gao Xiao-Wei, Luo Ying, Cai Yan, Zhou Kun, Du An-Jie, Zhao Yong
Medical College of Shihezi University, Shihezi 832000, Xinjiang Uygur Autonomous Region, China ; Ophthalmic Center, No.474 Hospital of Chinese PLA, Urumqi 830013, Xinjiang Uygur Autonomous Region, China.
Ophthalmic Center, No.474 Hospital of Chinese PLA, Urumqi 830013, Xinjiang Uygur Autonomous Region, China.
Int J Ophthalmol. 2014 Apr 18;7(2):198-204. doi: 10.3980/j.issn.2222-3959.2014.02.03. eCollection 2014.
To investigate the effect of intravitreal injection administered sorafenib, a multikinase inhibitor, in a rat model of oxygen-induced retinopathy (OIR).
Seven-day-old Sprague-Dawley rats (n=144) were randomly assigned to six groups. Group A received normal partial oxygen pressure and groups B, C, D, E and F were exposed to hyperoxia (75±2)% from postnatal 7d (P7) to P12 to induce retinopathy of prematurity. The rats in groups C, D, E and F were received intravitreal injections of either vehicle (DMSO) or sorafenib at P12 (5, 20 and 80 µg, respectively). Then they returned to normoxia after P12. The retinas were whole-mounted and imaged with a confocal microscopy. The vascular branching points were counted to quantify neovascularization at P17. Cross-sections of the retina were stained with hematoxylin and eosin (HE). The nuclei of new vessels breaking the internal limiting membrane were counted to quantify the proliferative neovascular response.
The retinal vessel in groups B and C turned into tortuosity and a great deal of neovascularization were observed. Sorafenib-treated rats had significantly less neovascularization as compared with vehicle-treated and control rats in a dose dependent manner (P<0.05). The number of vascular branching points in A, B, C, D, E and F were 16.50±3.90, 37.44±6.47, 37.08±5.10, 30.80±6.85, 26.08±5.08 and 19.83±3.51, respectively. The number of the nuclei of retinal new vessel in A, B, C, D, E and F were 0.22±0.42, 35.66±4.70, 35.30±4.54, 27.30±4.28, 21.41±3.53, and 7.41±2.87, respectively. There were significant difference between each group (P<0.05) except groups B and C.
In the rat OIR model, sorafenib could inhibit retinal neovascularization in a dose dependent manner.
研究玻璃体内注射多激酶抑制剂索拉非尼对氧诱导性视网膜病变（OIR）大鼠模型的影响。
将7日龄的Sprague-Dawley大鼠（n = 144）随机分为6组。A组接受正常分压氧气，B、C、D、E和F组从出生后7天（P7）至P12暴露于高氧（75±2）%以诱导早产儿视网膜病变。C、D、E和F组的大鼠在P12时接受玻璃体内注射溶剂（二甲基亚砜）或索拉非尼（分别为5、20和80μg）。然后在P12后恢复至常氧环境。将视网膜进行铺片并用共聚焦显微镜成像。在P17时计数血管分支点以量化新生血管形成。视网膜横断面用苏木精和伊红（HE）染色。计数突破内界膜的新生血管细胞核以量化增殖性新生血管反应。
B组和C组的视网膜血管迂曲，观察到大量新生血管形成。与溶剂处理组和对照组大鼠相比，索拉非尼处理的大鼠新生血管形成明显减少，呈剂量依赖性（P<0.05）。A、B、C、D、E和F组的血管分支点数分别为16.50±3.90、37.44±6.47、37.08±5.10、30.80±6.85、26.08±5.08和19.83±3.51。A、B、C、D、E和F组视网膜新生血管细胞核数分别为0.22±0.42、35.66±4.70、35.30±4.54、27.30±4.28、21.41±3.53和7.41±2.87。除B组和C组外，各组之间存在显著差异（P<0.05）。
在大鼠OIR模型中，索拉非尼可剂量依赖性地抑制视网膜新生血管形成。
