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

作　　者：张建忠 陈丹[3] 许政[1] 王君玉 韩凯伟 侯立军 ZHANG Jian-zhong;CHEN Dan;XU Zheng;WANG Jun-yu;HAN Kai-wei;HOU Li-jun(Department of Neurosurgery,Neurosurgery Research Institution of Shanghai,Changzheng Hospital,Naval Miliary Medical University(The Second Military Medical University),Shanghai,200003,China;Department of Neurosurgery,Naval Special Medical Center,Naval Military Medical University(The Second Military Medical University),,Shanghai,200052,China;Department of Orthopedics,Naval Special Medical Center,Naval Military Medical University(The Second Military Medical University),Shanghai,200052,China)

机构地区：[1]上海市海军军医大学附属长征医院神经外科,上海200003 [2]上海市海军军医大学附属海军特医学中心神经外科(解放军第455医院神经外科),上海200052 [3]上海市海军军医大学附属海军特医学中心骨科(解放军第455医院骨科),上海200052

出　　处：《现代生物医学进展》2020年第18期3401-3406,共6页Progress in Modern Biomedicine

基　　金：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)。

摘　　要：目的:明确mi R-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mi R-448-3p表达;qRT-PCR和western blot用于检测KLF5 m RNA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mi R-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mi R-448-3p的直接靶点。此外,mi R-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。mi R-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mi R-448-3p处理后表达显著降低。我们还发现mi R-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mi R-448-3p所抑制。结论:研究结果表明,mi R-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。Objective:To determine the function of mi R-448-3 p 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 mi R-448-3 p was detected by qRT-PCR assay,and KLF5 m RNA 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 mi R-448-3 p was decreased and KLF5 was increased in IA rats.We showed that KLF5 was a direct target of mi R-448-3 p in SMCs.In addition,aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the mi R-448-3 p-treated IA rats.mi R-448-3 p treatment protected the wall thickness ratio and inhibited macrophage infiltration after IA induction.IA caused an increase in KLF5 expression and mi R-448-3 p alleviated KLF5 expression Moreover,the anti-inflammatory effect of mi R-448-3 p 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 mi R-448-3 p.Conclusions:All data indicate that mi R-448-3 p have the inhibitory role in IA progression,suggesting that mi R-448-3 p is crucial for preventing the development of IA through suppressing the macrophage-mediated inflammation.

关 键 词：颅内动脉瘤 miR-448-3p KLF5 巨噬细胞 炎症 

分 类 号：R-33[医药卫生] R7