HIF-1α干扰RNA抑制早产儿视网膜病小鼠模型视网膜新生血管形成的研究  被引量:5

HIF-1α siRNA reduces retinal neovascularization in a mouse model of retinopathy of prematurity

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作  者:许惠卓[1] 刘双珍[1] 熊思齐[1] 夏晓波[1] 

机构地区:[1]中南大学湘雅医院眼科,湖南长沙410008

出  处:《中国当代儿科杂志》2011年第8期680-683,共4页Chinese Journal of Contemporary Pediatrics

基  金:国家自然科学基金(30471853)

摘  要:目的探讨特异性抑制缺氧诱导因子-1α(HIF-1α)的表达对早产儿视网膜病变(retinopathy of pre-maturity,ROP)小鼠模型视网膜新生血管的抑制作用。方法新生C57BL/6J小鼠48只,随机分为实验组和对照组(每组24只),采用Smith方法制备ROP模型。生后12 d时实验组玻璃体腔注射HIF-1α特异性小片段干扰RNA表达载体pSUPERH1-siHIF-1α,同时对照组玻璃体注射空载体。Western blot检测两组小鼠视网膜HIF-1α和血管内皮生长因子(VEGF)的表达,FITC-Dextran荧光照影视网膜铺片和组织切片观察两组小鼠视网膜新生血管和新生血管内皮细胞核数目的差异。结果实验组小鼠HIF-1α和VEGF的表达较对照组明显下降(P<0.01);实验组突破视网膜内界膜血管内皮细胞核数较对照组明显减少(P<0.01)。结论特异性抑制HIF-1α能有效抑制ROP视网膜新生血管的形成。Objective To study the inhibition effect of HIF-1α specific siRNA expression vector pSUPERH1-siHIF-1α on retinal neovascularization in a mouse model of retinopathy of prematurity(ROP). Methods The mouse model of ROP was prepared by the method Smith described.Forty-eight ROP mice were randomly divided into two groups: an experimental group that was intravitreously injected with pSUPERH1-siHIF-1α and a control group that was injected with pSUPER retro vector.The levels of HIF-1α and vascular endothelia growth factor(VEGF) in the retina were examined by Western blot.The retinal neovascularization was evaluated by angiography using FITC Dextran and quantitated histologically. Results The levels of HIF-1α and VEGF in the retina in the experimental group were reduced 90% and 65% respectively compared with those in the control group.Meanwhile,the number of retinal neovascular endothelial nucleus outbreaking the inner limit membrane in the experimental group was significantly reduced compared with that in the control group. Conclusions The development of retinal neovascularization of ROP can be markedly inhibited by RNA interference targeting HIF-1α.

关 键 词:缺氧诱导因子1Α 早产儿视网膜病变 RNA干扰 视网膜新生血管 小鼠 

分 类 号:R774.1[医药卫生—眼科]

 

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