| 张建忠,陈 丹,许 政,王君玉,韩凯伟,侯立军.miR-448-3p通过调节KLF5的表达抑制颅内动脉瘤进展[J].,2020,(18):3401-3406 |
| miR-448-3p通过调节KLF5的表达抑制颅内动脉瘤进展 |
| miR-448-3p Suppressed Intracranial Aneurysm by Inhibiting KLF5 Expression |
| 投稿时间：2020-02-28 修订日期：2020-03-23 |
| DOI：10.13241/j.cnki.pmb.2020.18.001 |
| 中文关键词: 颅内动脉瘤 miR-448-3p KLF5 巨噬细胞 炎症 |
| 英文关键词: Aneurysm miR-448-3p KLF5 Macrophage Inflammation |
| 基金项目:上海市长宁区科学技术委员会基金项目（CNKW2016Y29)；国家自然科学基金青年科学基金项目（ 81801141） |
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| 中文摘要: |
| 摘要 目的：明确miR-448-3p对颅内动脉瘤发展的影响。方法：我们通过结扎左侧肾动脉和左侧颈总动脉的方法建立大鼠IA模型；qRT-PCR用于检测miR-448-3p表达；qRT-PCR和western blot用于检测KLF5 mRNA和蛋白表达；qRT-PCR和ELISA法用于检测炎症因子水平。结果：我们发现IA诱导大鼠中miR-448-3p表达下调，而KLF5表达上调。我们发现并鉴定出KLF5是平滑肌细胞中miR-448-3p的直接靶点。此外，miR-448-3p处理使得IA诱导4周后动脉瘤大小和瘤腔截面积变小。miR-448-3p处理保护了IA诱导后的壁厚比，抑制了巨噬细胞浸润。IAs引起KLF5表达显著增加，被miR-448-3p处理后表达显著降低。我们还发现miR-448-3p在脂多糖诱导的RAW 264.7巨噬细胞中具有抗炎作用。脂多糖促进KLF5、MMP2、MMP9的表达水平，但却被miR-448-3p所抑制。结论：研究结果表明，miR-448-3p可以抑制IA的进展，其机制可能是通过下调KLF5的介导的炎症反应。 |
| 英文摘要: |
| ABSTRACT Objective: To determine the function of miR-448-3p inintracranial aneurysm (IA) development. Methods: We created a rat model of IA by ligating the left renal artery and the left common carotid artery. The expression of miR-448-3p was detected by qRT-PCR assay, and KLF5 mRNA and protein levels were measured by qRT-PCR and western blot. Inflammatory cytokines were measured by qRT-PCR and ELISA assay. Results: We found that miR-448-3p was decreased and KLF5 was increased in IA rats. We showed that KLF5 was a direct target of miR-448-3p in SMCs. In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p-treated IA rats. miR-448-3p treatment protected the wall thickness ratio and inhibited macrophage infiltration after IA induction. IA caused an increase in KLF5 expression and miR-448-3p alleviated KLF5 expression Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. Conclusion: All data indicate that miR-448-3p have the inhibitory role in IA progression, suggesting that miR-448-3p is crucial for preventing the development of IA through suppressing the macrophage-mediated inflammation. |
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