中国医学科学院学报

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中国医学科学院学报

中国医学科学院学报 ›› 2013, Vol. 35 ›› Issue (1): 29-35.doi: 10.3881/j.issn.1000-503X.2013.01.006

• 论著 • 上一篇    下一篇

C-C趋化因子受体2在盐敏感性高血压所致肾脏损害中的作用

孙邈1, 2,崔琳1,刘卫红1,高原1,沈思1,朱明军1,王幼平1   

  1. 1河南中医学院第一附属医院中心实验室及心脏中心,郑州 4500002河南中医学院中医内科学,郑州 450008
  • 收稿日期:2012-05-14 出版日期:2013-03-07 发布日期:2013-03-07
  • 通讯作者: 王幼平 电话:0371-66248345, 电子邮件: wangyouping2@gmail.com
  • 基金资助:
    国家自然科学基金(81170243)

Role of Chemokine Receptor 2 in Renal Damage Induced byDeoxycorticosterone Acetate-salt Hypertension

SUN Miao1, 2, CUI Lin1, LIU Wei-Hong1, GAO Yuan1, SHEN Si1, ZHU Ming-Jun1, WANG You-ping1   

  1. 1Central Laboratory and Division of Cardiology, the First Affiliated Hospital of Henan Universityof Traditional Chinese Medicine, Zhengzhou 450000, China2Internal Medicine of Traditional Chinese Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China
  • Received:2012-05-14 Online:2013-03-07 Published:2013-03-07
  • Supported by:
    Supported by the National Natural Sciences Foundation of China(81170243);第一、二位作者对本文贡献相同The first two authors contributed equally to this article

摘要: 目的 探讨C-C趋化因子受体2(CCR2)在盐敏感性高血压所致肾脏损害中的作用。方法 通过切除小鼠左侧肾脏、皮下包埋醋酸脱氧皮质酮(DOCA)和饮用盐水制备盐敏感性高血压小鼠模型,DOCA-盐高血压小鼠分为模型组和CCR2受体阻断剂组,分别皮下注射溶媒和特异性的CCR2受体阻断剂RS504393,对照组小鼠仅左肾切除和给予正常饮用水。检测动脉收缩压、24 h尿白蛋白排泄量、8-异构前列腺素排泄量、肌酐清除率、肾小球纤维样硬化指数、单核/巨噬细胞浸润程度。结果 与对照组相比,模型组血压升高、24 h尿白蛋白和8-异构前列腺素排泄量增加、肌酐清除率下降、肾脏有较明显的肾小球纤维样硬化和肾小管间质损害,并伴有明显的单核/巨噬细胞浸润(P<0.05)。RS504393能显著抑制上述异常变化(P<0.05),使各项肾功能和肾形态学指标基本恢复正常,但RS504393对血压无影响。结论 CCR2受体阻断剂可抑制DOCA-盐高血压所致肾脏损害,CCR2受体介导的单核/巨噬细胞浸润在盐敏感性高血压诱导的肾脏损害中发挥重要作用。   

关键词: 盐敏感性高血压, 肾脏损害, C-C趋化因子受体2, 阻断剂, 单核/巨噬细胞

Abstract: Objective To determine the role of chemokine receptor 2 (CCR2) in the development of salt-sensitive hypertension-induced renal damage. Methods We investigated the renal damage induced by uninephrectomy and deoxycorticosterone acetate (DOCA)-salt in mice treated with or without a selective CCR2 antagonist RS504393 for 4 weeks. Sham mice underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration were measured. Results DOCA-salt treatment led to increased systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration compared with the sham mice (P<0.05). All of them were prevented by CCR2 inhibition (P<0.05). Conclusion Blockade of CCR2 prevents renal damage induced by DOCA-salt treatment, suggesting that CCR2-mediated monocyte/macrophage infiltration may contribute to salt-sensitive hypertension-induced renal injury.

Key words: salt-sensitive hypertension, renal injury, chemokine receptor 2, antagonist, monocyte/macrophage

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