血管紧张素(1-7)通过p53/Drp1轴对血管紧张素Ⅱ诱导的血管内皮细胞衰老的影响
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(1.山西医科大学,山西省太原市 030001;2.山西医科大学第二医院心血管内科, 山西省太原市030013)

作者简介:

郭春玲,硕士研究生,研究方向为冠心病的基础与临床,E-mail为guochunling2018@163.com。通信作者李保,博士,主任医师,教授,博士研究生导师,研究方向为心血管疾病基础研究及临床诊治,E-mail为libaoxys@163.com。

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国家自然科学基金青年项目(81900275);山西省青年科技研究基金面上项目(201801D221273);山西省重点研发计划项目(201803D31116)


Effect of angiotensin(1-7) on angiotensin Ⅱ-induced vascular endothelial cell senescence by the p53/Drp1 pathway
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1, LU Zhaoyang2, YANG Bin2, RONG Shuling2, WANG Ruiying2, YANG Zhiming2, LI Bao2 (1.Shanxi Medical University, Taiyuan, Shanxi 030001, China;2.Department of Cardiology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030013, China)

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    摘要:

    目的 观察血管紧张素(1-7)[Ang(1-7)]对血管紧张素Ⅱ(AngⅡ)诱导的人脐静脉内皮细胞(HUVEC)衰老的作用及机制。方法 体外用含有10%胎牛血清(FBS)的DMEM培养基培养HUVEC 48 h,随机分为对照组、Ang(1-7)组(1 μmol/L)、AngⅡ组(1 μmol/L)和AngⅡ+Ang(1-7)组。通过细胞衰老β-半乳糖苷酶(SA-β-Gal)染色试剂盒检测各组衰老细胞数量(光学显微镜观察),通过活性氧检测试剂盒测定各组细胞活性氧(ROS)的水平,通过Western blot检测各组细胞p53和动力蛋白相关蛋白1(Drp1)的表达。结果 与对照组比较,AngⅡ组SA-β-Gal染色阳性细胞明显增多(P<0.001),细胞ROS水平增加(P<0.001),p53及Drp1蛋白表达量明显增加(P<0.01)。与AngⅡ组比较,AngⅡ+Ang(1-7)组SA-β-Gal染色阳性细胞率(P<0.01)、细胞ROS水平(P<0.001)、p53及Drp1蛋白表达量(P<0.05)均降低。结论 Ang(1-7)可能通过影响p53/Drp1通路,抑制HUVEC内ROS生成,减轻AngⅡ诱导的HUVEC衰老。

    Abstract:

    Aim The purpose of this study was to observe the effect and mechanism of angiotensin(1-7)(Ang(1-7)) on angiotensin Ⅱ(AngⅡ)-induced senescence of human umbilical vein endothelial cell(HUVEC). MethodsHUVEC were cultured in vitro with DMEM high glucose medium containing 10%fetal bovine serum (FBS) for 48 hours and randomly divided into control group, Ang(1-7) group (1 μmol/L), AngⅡ group (1 μmol/L), and AngⅡ+Ang(1-7) group. Cell senescence β-galactosidase(SA-β-Gal) staining kits were used to detect the number of senescent cell in each group (observed under an optical microscope); reactive oxygen species (ROS) levels were measured using reactive oxygen detection kits, and p53 and dynamin related protein-1(Drp1) expression in each group were detected by Western blot.Results Compared with the control group, both SA-β-Galpositive cell and ROS levels in the AngⅡ group were significantly increased(P<0.001), and p53 and Drp1 protein expression in the cell were significantly increased (P<0.01). Compared with AngⅡ group, SA-β-Galpositive cell(P<0.01), ROS levels(P<0.001), p53 and Drp1 protein expression(P<0.05) were decreased in AngⅡ+Ang(1-7) group. Conclusion Ang(1-7) may inhibit the ROS generation in HUVEC by affecting the p53/Drp1 pathway, and reverse the aging of HUVEC induced by AngⅡ.

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郭春玲,逯朝阳,杨滨,荣书玲,王瑞英,杨志明,李保.血管紧张素(1-7)通过p53/Drp1轴对血管紧张素Ⅱ诱导的血管内皮细胞衰老的影响[J].中国动脉硬化杂志,2020,28(11):960~965.

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  • 收稿日期:2019-12-09
  • 最后修改日期:2020-05-01
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  • 在线发布日期: 2020-11-30