Regression of Intracranial Aneurysms by Simultaneous Inhibition of Nuclear Factor-κB and Ets With Chimeric Decoy Oligodeoxynucleotide Treatment
Regression of Intracranial Aneurysms by Simultaneous Inhibition of Nuclear Factor-κB and Ets With Chimeric Decoy Oligodeoxynucleotide Treatment
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DOI：
10.1227/neu.0b013e318246a390
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发表时间：
2012-06-01
期刊：
影响因子：
4.8
通讯作者：
Miyamoto, Susumu
中科院分区：
文献类型：
--
作者：
Aoki, Tomohiro;Kataoka, Hiroharu;Miyamoto, Susumu
背景技术背景：尽管由于颅内动脉瘤（IA）引起的蛛网膜下腔出血的死亡率和发病率很高，但没有有效的药物治疗来预防IA的破裂。最近的研究表明核因子-κ B参与了促炎基因的反式激活目的：研究同时抑制NF-κ B和Ets-1的嵌合诱骗寡核苷酸（decoy oligodeoxynucleotides，ODNs）对大鼠IA形成和扩大的逆转作用。在IA诱导后一个月，用NF-κ B诱饵ODN或嵌合诱饵ODN处理大鼠。大小，中膜厚度，巨噬细胞浸润，和胶原蛋白的生物合成在IA walls.RESULTS：治疗嵌合诱饵ODNs减少IA的大小和增厚的IA壁预先存在的IA在大鼠模型中诱导，虽然治疗NF-κ B诱饵ODNs未能回归预先存在的IA。嵌合诱饵ODN处理的大鼠表现出单核细胞趋化蛋白-1和巨噬细胞浸润IA壁的表达减少。此外，减少胶原蛋白生物合成IA walls.CONCLUSION：嵌合诱饵ODN治疗group.CONCLUSION：结果表明，一种微创的分子治疗靶向抑制NF-κ B和ets-1的IA在人类的可能性。
BACKGROUND: Despite a high mortality and morbidity of subarachnoid hemorrhage due to an intracranial aneurysm (IA), there is no effective medical treatment to prevent the rupture of IAs. Recent studies have revealed the involvement of the transactivation of proinflammatory genes by nuclear factor-kappa B (NF-kappa B) and Ets-1 in the pathogenesis of IA formation and enlargement.OBJECTIVE: To examine the regressive effect of chimeric decoy oligodeoxynucleotides (ODNs), which simultaneously inhibit NF-kappa B and Ets-1, on IA development in the rat model.METHODS: One month after IA induction, rats were treated with NF-kappa B decoy ODNs or chimeric decoy ODNs. Size, media thickness, macrophage infiltration, and collagen biosynthesis in IA walls were analyzed in both groups.RESULTS: The treatment with chimeric decoy ODNs decreased IA size and thickened IA walls of preexisting IAs induced in the rat model, although the treatment with NF-kappa B decoy ODNs failed to regress preexisting IAs. Chimeric decoy ODN-treated rats exhibited decreased expression of monocyte chemotactic protein-1 and macrophage infiltration in IA walls. In addition, decreased collagen biosynthesis in IA walls was ameliorated in the chimeric decoy ODN-treated group.CONCLUSION: The results suggest the possibility of a minimally invasive molecular therapy targeting the inhibition of NF-kappa B and ets-1 for IAs in humans.