中国医科大学学报

中国医科大学学报
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中国医科大学学报 ›› 2018, Vol. 47 ›› Issue (8): 692-695,700.doi: 10.12007/j.issn.0258-4646.2018.08.005

• 论著 • 上一篇    下一篇

醛固酮诱导p21依赖性肾脏衰老的机制

范愈燕1, 孙永新2, 刘青山3, 周亦伦4, 李平5, 梁秉中6   

  1. 1. 首都医科大学附属天坛医院疼痛科, 北京 100050;
    2. 中国医科大学附属第一医院康复科, 沈阳 110001;
    3. 中央民族大学中国少数民族传统医学研究院, 北京 100030;
    4. 首都医科大学附属天坛医院肾内科, 北京 100050;
    5. 中日友好医院临床医学研究所, 北京 100029;
    6. 香港中文大学中医中药研究所, 香港 999077
  • 收稿日期:2018-02-07 出版日期:2018-08-30 发布日期:2018-08-17
  • 通讯作者: 范愈燕 E-mail:fanyy2002@hotmail.com
  • 作者简介:范愈燕(1970-),女,副主任医师,博士.
  • 基金资助:
    国家自然科学基金(81774214)

Aldosterone Stimulates p21-dependent Cellular Senescence in the Kidney

FAN Yuyan1, SUN Yongxin2, LIU Qingshan3, ZHOU Yilun4, LI Ping5, LIANG Bingzhong6   

  1. 1. Department of Pain, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
    2. Department of Rehabilitation, The First Hospital, China Medical University, Shenyang 110001, China;
    3. Institute of Chinese Minority Traditional Medicine, Minzu University of China, Beijing 100081, China;
    4. Department of Nephrology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
    5. Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 100029, China;
    6. Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China
  • Received:2018-02-07 Online:2018-08-30 Published:2018-08-17

摘要: 目的 探讨p21是否是醛固酮诱导肾脏衰老并引起肾功能损害的重要机制。方法 采用醛固酮刺激永生化人近曲小管细胞及p21(-/-)小鼠,观察衰老标记物β-Galp21基因的变化。结果 醛固酮可以诱导永生化人近曲小管细胞β-Gal表达和p21基因表达水平异常升高,p21基因敲除明显抑制了β-Gal表达及肿瘤坏死因子αTNF-α)和胶原蛋白基因表达。正常FVB小鼠及p21(-/-)小鼠同时皮下泵入醛固酮,结果发现,正常FVB小鼠肾脏皮质β-Gal及胶原蛋白基因高表达,而p21(-/-)小鼠肾脏皮质内的表达则较低。结论 醛固酮诱导的TNF-α和胶原蛋白表达变化可能是p21依赖的细胞衰老的机制。

关键词: 醛固酮, 永生化人近曲小管细胞, p21(-/-)小鼠、肾脏衰老

Abstract: Objective To investigate whether aldosterone-induced p21-dependent renal senescence affects the development of renal injury. Methods In vitro,immortalized human proximal tubular cells were stimulated by aldosterone;in vivo,aldosterone induced renal senescence genes in normal FVB mice and p21(-/-)mice. Results Aldosterone induced elevated expression of the β-Gal,p21,TNF-α, and two collagen genes in immortalized human proximal tubule cells. These genes were significantly inhibited by knock-out of p21. At the same time,normal FVB mice and p21(-/-)mice were stimulated through subcutaneous administration of aldosterone using a mini-pump. Increased expression of β-Gal,TNF-α,and the two collagen genes was seen in the kidney cortex of normal FVB mice,but not in the kidney cortex of p21(-/-)mice. Conclusion Aldosterone-induced changes in TNF-α and collagen expression may be involved in p21-dependent cell senescence.

Key words: aldosterone, human proximal tubular cells, p21(-/-) mice, cell senescence

中图分类号: 

  • R363.2
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