miR-17-5p在动脉粥样硬化小鼠中的作用机制研究  

Study on the mechanism of miR-17-5p in atherosclerotic mice

作　　者：谭力力[1] 刘丽敏[1] Tan Lili;Liu Limin(Dept of Vasculocardiology,The Second Hospital of Shenyang Medical College,Shenyang 110002)

机构地区：[1]沈阳医学院附属第二医院心血管内科,沈阳110002

出　　处：《安徽医科大学学报》2018年第6期889-893,共5页Acta Universitatis Medicinalis Anhui

基　　金：辽宁省自然科学基金(编号:201602728);沈阳市科技计划项目(编号:F16-206-9-17;F14-158-9-27)

摘　　要：目的探讨miR-17-5p在动脉粥样硬化发展中对组织炎症反应及氧化应激水平的影响。方法高脂喂养ApoE-/-小鼠12周构建动脉粥样硬化(AS)模型,尾静脉注射miR-17-5p拮抗剂。HE染色观察主动脉的病理变化;TUNEL染色观察细胞凋亡,Western blot检测凋亡相关蛋白的表达情况;ELISA检测炎症因子的表达。通过检测丙二醛(MDA)含量、超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)的活性评估氧化应激水平。结果抑制miR-17-5p减轻了AS小鼠主动脉的病变程度,减少了主动脉细胞凋亡,同时下调了Bax、cleaved-caspase-3、cleaved-PARP的表达,上调了Bcl-2蛋白表达。抑制miR-17-5p后,AS小鼠主动脉TNF-α、IL-6水平下降,IL-10水平上升,同时MDA含量及MPO活性受到抑制,SOD活性上调。结论抑制miR-17-5p可以通过减轻动脉粥样硬化小鼠主动脉的炎症反应和氧化应激水平缓解动脉粥样硬化病变。miR-17-5p可能是治疗动脉粥样硬化的潜在靶点。Objective To investigate the effect of miR-17-5 p on the inflammatory response and oxidative stress in the development of atherosclerosis. Methods ApoE-/-mice were fed with high fat diet for 12 weeks to construct atherosclerosis（ AS） model,and then miR-17-5 p antagonist was injected to the caudal vein of mice subsequently. HE staining was used to observe the pathological changes of the aorta. The apoptosis of aorta cells was detected by TUNEL staining. Western blot was used to detect the expression of apoptosis-related proteins and the expression of inflammatory cytokines weas detected by ELISA. Oxidative stress were assessed by malondialdehyde（ MDA） levels and the activity of superoxide dismutase（ SOD） and myeloperoxidase（ MPO）. Results Inhibition of miR-17-5 p alleviated the aortic lesion and apoptosis in AS mice,reduced the expression of Bax,cleavedcaspase-3 and cleaved-PARP and up-regulated the expression of Bcl-2. After inhibition of miR-17-5 p,the levels of TNF-α and IL-6 in AS mice decreased,and the level of IL-10 increased. Inhibition of miR-17-5 p also resulted in decrease in MDA and MPO activity,but increase in SOD activity. Conclusion Inhibition of miR-17-5 p can attenuate atherosclerotic lesions by reducing the inflammatory response and oxidative stress in the aorta of atherosclerotic mice. MiR-17-5 p may be a potential target for the treatment of atherosclerosis.

关 键 词：动脉粥样硬化 炎症 氧化应激 miR-17-5p 

分 类 号：R543.5[医药卫生—心血管疾病]