增龄通过下调平滑肌细胞BKCa通道α和β1亚基表达改变肠系膜动脉舒缩性
DOI:
作者:
作者单位:

作者简介:

通讯作者:

基金项目:

国家自然科学基金(31371201),新世纪优秀人才支持计划(NCET-11-0850),北京市自然科学基金(5132017),国家科技支撑计划课题资助项目(2012BAK21B03)


Aging Changes the Vascular Contractility in the Rat Mesenteric Arteries by Downregulation of the α-and β1-subunit Expression of BKCa Channels in Smooth Muscle Cells
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
    摘要:

    目的 探讨增龄对大鼠肠系膜动脉平滑肌细胞大电导钙激活钾通道 (BKCa) α和β1亚基蛋白表达的影响。方法 选用不同年龄雄性Wistar大鼠,分为青年组(4~5月龄)、中年组(15~16月龄)和老年组(22~24月龄)。分别进行在体血压监测和离体去内皮血管张力测定,并采用蛋白免疫印迹分析观察肠系膜动脉平滑肌细胞BKCa通道α和β1亚基的表达。结果 增龄导致大鼠收缩压和脉压显著增大。去甲肾上腺素诱发各组肠系膜动脉收缩,并呈浓度依赖性,增龄导致血管对去甲肾上腺素的敏感性(pD2)和最大收缩反应降低;BKCa通道选择性阻断剂Iberiotoxin诱发各组血管张力增高,但增高幅度青年组>中年组>老年组。蛋白免疫印迹分析显示α和β1亚基均随增龄下降,但β1亚基下降幅度显著大于α亚基。结论 增龄诱导大鼠肠系膜动脉BKCa通道在血管张力维持中的贡献下降,其分子机制可能为增龄诱发的α和β1亚基表达非平行性下调(β1亚基下调更为显著)。

    Abstract:

    Aim To investigate the effects of aging on the molecular expression of α- and β1-subunit of large-conductance Ca2+-activated K+ (BKCa) channels in rat mesenteric arterial smooth muscle cells. Methods Young (4~5 months), middle-aged (15~16 months), and old (22~24 months) male Wistar rats were used. In vivo blood pressure and in vitro endothelium-removed mesenteric arterial tension were measured. Immunohistochemistry and Western Blot assay were also conducted. Results The systolic blood pressure and pulse pressure were significantly increased with aging. The vascular tone caused by norepinephrine (NE) strongly increased in a concentration dependent manner in each group, and aging reduced the sensitivity to NE in mesenteric arteries (MA). Selective BKCa channel blocker (Iberiotoxin) induced a marked increase of vascular tension in MA in all three age groups. However, these effects were greatly decreased in old animals. Western Blot showed that the protein expression of BKCa α- and β1-subunit was significantly reduced with aging, and the suppression of β1 subunits was larger than that of α subunits. Conclusions These data suggest that aging induces decrease of molecular expression of α- and β1-subunit of BKCa channels in MA myocytes, in which the suppression of β1-subunit is more pronounced than α-subunit. This unparallel downregulation of two subunits may be the mechanism underlying the aging-associated decrease of BKCa channel contribution in regulating MA basal tone.

    参考文献
    相似文献
    引证文献
引用本文

张严焱,张寒梦,石丽君,赵虎成.增龄通过下调平滑肌细胞BKCa通道α和β1亚基表达改变肠系膜动脉舒缩性[J].中国动脉硬化杂志,2014,22(8):757~762.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:2014-01-06
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: