基因沉默
外渗
缺血
埃文斯蓝
小干扰RNA
医学
免疫印迹
转染
封堵器
RNA干扰
体内
病理
基质金属蛋白酶
药理学
内科学
大脑中动脉
癌症研究
化学
核糖核酸
生物
细胞生物学
基因
紧密连接
生物化学
生物技术
作者
Qin Hu,Chunhua Chen,Junhao Yan,Xiaomei Yang,Xiaoming Shi,Jing Zhao,Jiliang Lei,Lei Yang,Ke Wang,Lin Chen,Hongyun Huang,Jing‐Yan Han,Junyi Zhang,Changman Zhou
标识
DOI:10.1016/j.expneurol.2008.11.007
摘要
RNA interference appears to have a great potential not only as an in vitro target validation, but also as a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene. We hypothesize that MMP-9 siRNA can be effective as an MMP-9 protein inhibitor in a rat focal ischemia model. Male Sprague–Dawley rats (156) were subjected to 2 h of middle cerebral artery occlusion (by using the suture insertion method) followed by 24 h of reperfusion. In the treatment group, 5 μl MMP-9 siRNA was administrated by intracerebroventricular injection within 60 min after 2 h of focal ischemia. The siRNA transfection was demonstrated by fluorescence conjugated siRNA. Treatment with MMP-9 siRNA produced a significant reduction in the cerebral infarction volume, brain water content, mortality rate and accompanying neurological deficits. The followings were recorded: Evan's blue and IgG extravasation were reduced; the expression of MMP-9 mRNA and protein were significantly silenced; and immunohistochemistry and Western blot analysis revealed that the expression of MMP-9 and VEGF were reduced while occludin and collagen-IV were up-regulated in brain tissues. Our findings provide evidence that a liposomal formulation of siRNA might be used in vivo to silence the MMP-9 gene and could potentially serve as an important therapeutic alternative in patients with cerebral ischemia.
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