文章摘要
徐敬轩,张 勖,杨 岩,邓国棋,栾新平.miR-19靶向PTEN并介导HMGB1影响小鼠动脉粥样硬化进程的机制研究[J].,2022,(6):1013-1017
miR-19靶向PTEN并介导HMGB1影响小鼠动脉粥样硬化进程的机制研究
Study on the Mechanism of miR-19 Targeting PTEN and Mediating HMGB1 to Affect the Process of Atherosclerosis in Mice
投稿时间:2021-08-27  修订日期:2021-09-23
DOI:10.13241/j.cnki.pmb.2022.06.003
中文关键词: miR-19  蛋白酪氨酸磷酸酶基因  高迁移率族蛋白B1  动脉粥样硬化  小鼠
英文关键词: miR-19  PTEN  HMGB1  Atherosclerosis  Mice
基金项目:新疆维吾尔自治区自然科学基金项目(2019D01C235)
作者单位E-mail
徐敬轩 新疆医科大学第二附属医院神经外科 新疆 乌鲁木齐 830028 xujingxuan2020@163.com 
张 勖 新疆医科大学第二附属医院神经外科 新疆 乌鲁木齐 830028  
杨 岩 新疆医科大学第二附属医院神经外科 新疆 乌鲁木齐 830028  
邓国棋 新疆医科大学第二附属医院神经外科 新疆 乌鲁木齐 830028  
栾新平 新疆医科大学第二附属医院神经外科 新疆 乌鲁木齐 830028  
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中文摘要:
      摘要 目的:探究miR-19靶向PTEN并介导HMGB1影响小鼠动脉粥样硬化进程的机制研究。方法:SPF级C57BL/6J ApoE-/-雄性小鼠根据研究目的将实验小鼠分为对照组、AS模型组和miR-19抑制剂组。通过RT-PCR分析小鼠主动脉组织中miR-19的mRNA表达。通过蛋白印迹分析小鼠主动脉PTEN、HMGB1和AKT的蛋白表达。通过荧光素酶活性检测miR-19a与PTEN的靶向关系。通过组织学和红油O染色分析小鼠胸腹主动脉和主动脉窦中的AS斑块面积。通过RT-PCR分析小鼠主动脉主动脉弓内膜中促炎细胞因子和趋化因子的mRNA表达。通过蛋白印迹分析主动脉弓内膜中ICAM-1和VCAM-1的蛋白表达。结果:AS模型组miR-19mRNA表达较对照组升高(P<0.05),miR-19抑制剂组miR-19mRNA表达较AS模型组降低(P<0.05)。AS模型组PTEN蛋白表达较对照组降低,HMGB1和AKT蛋白表达较对照组升高(P<0.05),miR-19抑制剂组PTEN蛋白表达较AS模型组升高,miR-19抑制剂组HMGB1和AKT蛋白表达较AS模型组降低(P<0.05)。AS模型组主动脉和主动脉窦的斑块面积较对照组增加(P<0.05),miR-19抑制剂组主动脉和主动脉窦的斑块面积较AS模型组减少(P<0.05)。AS模型组TNF-α、IL-β、IL-6和CXCL2的mRNA表达较对照组升高(P<0.05),miR-19抑制剂组TNF-α、IL-6、IL-β和CXCL2的mRNA表达较AS模型降低(P<0.05)。AS模型组ICAM-1和VCAM-1的蛋白表达较对照组升高(P<0.05),miR-19抑制剂组ICAM-1和VCAM-1的蛋白表达较AS模型组降低(P<0.05)。结论:miR-19通过靶向调控PTEN表达激活HMGB1/PI3K/Akt信号通路,这可能会促进VSMCs的异常增殖、迁移和炎症反应,有助于AS的进展。
英文摘要:
      ABSTRACT Objective: To explore the mechanism of miR-19 targeting PTEN and mediating HMGB1 to affect the process of atherosclerosis in mice. Methods: SPF grade C57BL/6J ApoE-/- male mice were divided into control group, AS model group and miR-19 inhibitor group. The mRNA expression of miR-19 in mouse aorta tissue was analyzed by RT-PCR. The protein expression of PTEN, HMGB1 and AKT in mouse aorta was analyzed by Western blot. The targeting relationship between miR-19a and PTEN was detected by luciferase activity. The area of atherosclerotic plaque in mouse thoracic and abdominal aorta and aortic sinus was analyzed by histology and red oil O staining. The mRNA expression of proinflammatory cytokines and chemokines in the intima of the aortic arch of the mouse aorta was analyzed by RT-PCR. The protein expression of ICAM-1 and VCAM-1 in the intima of the aortic arch was analyzed by Western blot. Results: The expression of miR-19mRNA in the AS model group was higher than that in the control group(P<0.05), and the miR-19mRNA expression in the miR-19 inhibitor group was lower than that in the AS model group(P<0.05). The expression of PTEN protein in the AS model group was lower than that in the control group, the expression of HMGB1 and AKT protein was higher than that in the control group(P<0.05), and the expression of PTEN protein in the miR-19 inhibitor group was higher than that in the AS model group, the expression of HMGB1 and AKT protein in the miR-19 inhibitor group was lower than that in the AS model group(P<0.05). The plaque area of the aorta and aortic sinus in the AS model group was higher than that in the control group(P<0.05), and the plaque area of the aorta and aortic sinus in the miR-19 inhibitor group was lower than that in the AS model group(P<0.05). The mRNA expressions of TNF-α, IL-β, IL-6 and CXCL2 in the AS model group were higher than those in the control group(P<0.05), and the miR-19 inhibitor group TNF-α, IL-6, IL-β and CXCL2 mRNA expression was lower than that of AS model(P<0.05). The protein expression of ICAM-1 and VCAM-1 in the AS model group was higher than that in the control group(P<0.05), and the protein expression of ICAM-1 and VCAM-1 in the miR-19 inhibitor group was lower than that in the AS model group(P<0.05). Conclusion: miR-19 activates the HMGB1/PI3K/Akt signaling pathway through targeted regulation of PTEN expression, which may promote the abnormal proliferation, migration and inflammatory response of VSMCs, and contribute to the progress of AS.
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