首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (6): 725-730.doi: 10.3969/j.issn.1006-7795.2016.06.002

• 心血管疾病的病理生理机制 • 上一篇    下一篇

糖基化终末产物损伤冠状动脉平滑肌细胞Kv通道

苏文1, 李虹伟1, 陈晖1, 刘慧荣2, 黄海霞2, 李卫萍1   

  1. 1. 首都医科大学附属北京友谊医院心血管中心, 北京 100050;
    2. 首都医科大学基础医学院生理学与病理生理学系, 北京 100069
  • 收稿日期:2016-10-03 出版日期:2016-12-21 发布日期:2016-12-16
  • 通讯作者: 李卫萍 E-mail:xueer09@163.com
  • 基金资助:
    国家自然科学基金(30971240),北京市自然科学基金(7122053),北京市卫生系统高层次卫生技术人才资助项目(2013-3-060)

Advanced glycation end products impair voltage-gated K+ channels in coronary vascular smooth muscle cells

Su Wen1, Li Hongwei1, Chen Hui1, Liu Huirong2, Huang Haixia2, Li Weiping1   

  1. 1. Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
    2. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
  • Received:2016-10-03 Online:2016-12-21 Published:2016-12-16
  • Supported by:
    This study was supported by National Natural Science Foundation of China(30971240), Natural Science Foundation of Beijing (7122053),High-level Technical Talents Foundation in Beijing Health System (2013-3-060).

摘要: 目的 研究糖基化终末产物(advanced glycation end products,AGEs)对大鼠冠状动脉平滑肌细胞电压门控性钾离子(voltage-gated K+,Kv)通道电流的影响。方法 分离大鼠冠状动脉平滑肌细胞,分为空白对照组、糖基化牛血清白蛋白(AGE-bull serum albumin,AGE-BSA)组、AGE-BSA+抗AGE受体抗体(anti-receptor of AGEs immunoglobulin G,anti-RAGE IgG)组进行干预。采用膜片钳技术检测各组细胞Kv通道电流,采用Western blotting、实时荧光定量PCR方法检测各组细胞Kv1.2和Kv1.5通道蛋白及mRNA的表达。结果 AGE-BSA直接干预冠状动脉平滑肌细胞明显抑制了平滑肌细胞的Kv电流达32.7%,并使Kv1.2和Kv1.5通道蛋白及mRNA的表达明显下调。而给予anti-RAGE IgG预处理30 min后再加入AGE-BSA刺激,平滑肌细胞的Kv电流密度及Kv1.2和Kv1.5通道蛋白及mRNA的表达与空白对照组相比,差异无统计学意义。结论 AGEs通过结合RAGE损伤冠状动脉平滑肌细胞Kv通道。

关键词: 糖基化终末产物, 电压门控性钾离子通道, 冠状动脉平滑肌细胞, 糖基化终末产物受体

Abstract: Objective To investigate the role of advanced glycation end products (AGEs) in impairment of voltage-gated K+(Kv) channels in rat coronary vascular smooth muscle cells (VSMCs). Methods We isolated rat coronary VSMCs. The cells were incubated either in control medium, or medium with 100 μg/mL AGE-bovine serum albumin (AGE-BSA), or medium with 100 μg/mL AGE-BSA plus 100 μg/mL anti-receptor of AGEs immunoglobulin G (anti-RAGE IgG). Patch-clamp recording was used to assess the Kv currents. Western blotting and quantitative real-time PCR techniques were used to assess protein and mRNA expression of Kv 1.2 and Kv1.5. Results Incubation of VSMCs with AGE-BSA reduced Kv current density by 32.7% and decreased both protein and mRNA expression of Kv1.2 and Kv1.5 channels, whereas blocking AGE-BSA interacting with their receptors by preincubation with anti-RAGE IgG for 30 minutes prevented AGE-BSA-induced impairment of Kv channels.Conclusion AGEs impair Kv channels in coronary VSMCs by interacting with RAGE.

Key words: advanced glycation end products, voltage-gated K+ channels, coronary vascular smooth muscle cells, receptor of advanced glycation end products

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