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[缺氧诱导因子-1α小干扰RNA减少早产儿视网膜病变小鼠模型中的视网膜新生血管形成]

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

作者信息

Xu Hui-Zhuo, Liu Shuang-Zhen, Xiong Si-Qi, Xia Xiao-Bo

机构信息

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2011 Aug;13(8):680-3.

Abstract

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.

摘要

目的

研究低氧诱导因子-1α(HIF-1α)特异性小干扰RNA(siRNA)表达载体pSUPERH1-siHIF-1α对早产儿视网膜病变(ROP)小鼠模型视网膜新生血管形成的抑制作用。

方法

采用Smith描述的方法制备ROP小鼠模型。48只ROP小鼠随机分为两组:实验组玻璃体腔内注射pSUPERH1-siHIF-1α,对照组注射pSUPER逆转录载体。采用蛋白质免疫印迹法检测视网膜中HIF-1α和血管内皮生长因子(VEGF)的水平。利用异硫氰酸荧光素标记葡聚糖(FITC Dextran)血管造影术评估视网膜新生血管形成,并进行组织学定量分析。

结果

与对照组相比,实验组视网膜中HIF-1α和VEGF的水平分别降低了90%和65%。同时,实验组突破内界膜的视网膜新生血管内皮细胞核数量较对照组显著减少。

结论

靶向HIF-1α的RNA干扰可显著抑制ROP小鼠视网膜新生血管的形成。

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