[1]裴浩天,杨绍楠,马爱军,等. miR-155介导PI3K/Akt/mTOR自噬通路对ApoE-/-小鼠颈动脉粥样硬化斑块的影响[J].青岛大学学报(医学版),2018,54(03 ):253-256,262.[doi:10.11712/jms201803001]
 PEI Haotian,YANG Shaonan,MA Aijun,et al. EFFECT OF MIR-155-MEDIATED AUTOPHAGY VIA THE PI3K/AKT/MTOR PATHWAY ON CAROTID ATHEROSCLEROTIC PLAQUES IN APOE-/- MICE[J].JOURNAL OF QINGDAO UNIVERSITY (MEDICAL SCIENCES),2018,54(03 ):253-256,262.[doi:10.11712/jms201803001]
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 miR-155介导PI3K/Akt/mTOR自噬通路对ApoE-/-小鼠颈动脉粥样硬化斑块的影响()
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《青岛大学学报(医学版)》[ISSN:2096-5532/CN:37-1217/R]

卷:
第54卷
期数:
2018年03 期
页码:
253-256,262
栏目:
出版日期:
2018-05-29

文章信息/Info

Title:
 EFFECT OF MIR-155-MEDIATED AUTOPHAGY VIA THE PI3K/AKT/MTOR PATHWAY ON CAROTID ATHEROSCLEROTIC PLAQUES IN APOE-/- MICE
作者:
 裴浩天杨绍楠马爱军潘旭东董轶殷霜霜
 青岛大学附属医院神经内科,山东 青岛 266003
Author(s):
 PEI Haotian YANG Shaonan MA Aijun PAN Xudong DONG Yi YIN Shuangshuang
 Department of Internal Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
关键词:
 斑块动脉粥样硬化微RNAs自噬PI3K/Akt/mTOR信号通路
Keywords:
 plaque atherosclerotic microRNAs autophagy PI3K/Akt/mTOR signaling pathway
分类号:
R543.5;R342.2
DOI:
10.11712/jms201803001
文献标志码:
A
摘要:
 目的 探究miR-155对颈部动脉粥样硬化(AS)斑块的影响及其与内磷脂酰肌醇激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)自噬通路的关系。
方法 40只8周龄雄性ApoE-/-小鼠随机均分为对照组(普通饮食)、模型组(颈动脉套管术+高脂饮食+生理盐水)、miR-155上调组(颈动脉套管术+高脂饮食+miR-155-LV)和miR-155下调组(颈动脉套管术+高脂饮食+miR-155-RNAi-LV)。8周后股动脉取血检测血浆中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL)水平;取右颈动脉以苏木精-伊红(HE)染色方法观察颈动脉斑块生长情况;Western blot方法检测颈动脉中自噬相关蛋白(LC3-Ⅱ)及PI3K/Akt/mTOR信号通路蛋白的表达。
结果 高脂饮食组小鼠的TC、TG、LDL水平均明显高于对照组(F=7.02~48.81,P均<0.05),但高脂饮食的各组小鼠血脂水平差异无统计学意义(P均>0.05)。与对照组比较,模型组颈动脉管壁增厚、管腔狭窄;与模型组比较,miR-155上调组颈动脉中可见粥样硬化斑块进一步增大,管腔狭窄加重,而miR-155下调组颈动脉中局部斑块形成减小,管腔狭窄减轻。与对照组比较,模型组LC3-Ⅱ蛋白表达减少(t=16.31,P<0.05);与模型组比较,miR-155上调组中LC3-Ⅱ蛋白表达量明显减少(t=4.41,P<0.05),miR-155下调组中LC3-Ⅱ蛋白增加(t=4.52,P<0.05)。与对照组比较,模型组PI3K/Akt/mTOR信号通路中各蛋白表达量明显升高(t=3.30~9.05,P均<0.05),而上调miR-155后,该通路蛋白表达量进一步升高(t=3.12~3.31,P均<0.05);下调miR-155导致该通路蛋白表达明显下降(t=3.31~4.88,P均<0.05)。
结论 在ApoE-/-小鼠体内,靶向下调miR-155表达可抑制PI3K/Akt/mTOR信号通路促进自噬,减少颈部AS斑块的形成。
Abstract:
 Objective To investigate the effect of miR-155 on carotid atherosclerotic (AS) plaques and its association with autophagy via the phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway.
Methods Forty 8-week-old male ApoE-/- mice were randomly divided into control group (normal diet), model group (carotid collar + high-fat diet + normal saline), miR-155 up-regulation group (carotid collar + high-fat diet + miR-155-LV), and miR-155 down-regulation group (carotid collar + high-fat diet + miR-155-RNAi-LV). After 8 weeks, blood samples were taken from the femoral arteries to determine the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) cholesterol; the right carotid arteries were subject to hematoxylin and eosin staining to observe the growth of carotid artery plaques; Western blot was used to measure the expression of autophagy-associated protein light chain 3-Ⅱ (LC3-Ⅱ) and PI3K/Akt/mTOR signaling pathway-related proteins in carotid arteries.
Results The levels of TC, TG, and LDL in the high-fat diet groups were significantly higher than those in the control group (F=7.02-48.81,P<0.05), but there were no significant differences in the levels of blood lipids between high-fat diet groups (P>0.05). Compared with the control group, the model group had thickened carotid artery wall and narrowed carotid artery lumen. Compared with the model group, the miR-155 up-regulation group had further enlarged carotid atherosclerotic plaques and aggravated lumen stenosis, but the miR-155 down-regulation group had locally reduced carotid atherosclerotic plaques and relieved lumen stenosis. Compared with the control group, the model group had significantly reduced expression of LC3-Ⅱ (t=16.31,P<0.05). Compared with the model group, the expression of LC3-Ⅱ decreased significantly in the miR-155 up-regulation group (t=4.41,P<0.05), but increased significantly in the miR-155 down-regulation group (t=4.52,P<0.05). Compared with the control group, the model group showed significant increases in the expression levels of PI3K/Akt/mTOR pathway-related proteins (t=3.30-9.05,P<0.05); up-regulation of miR-155 further increased the expression of these proteins (t=3.12-3.31,P<0.05); however, down-regulation of miR-155 resulted in significant decreases in the expression of these proteins (t=3.31-4.88,P<0.05).
Conclusion Targeted down-regulation of miR-155 expression in ApoE-/- mice can reduce carotid atherosclerotic plaque formation by promoting autophagy via inhibiting the PI3K/Akt/mTOR signaling pathway.
更新日期/Last Update: 2018-06-05