解剖学报

解剖学报 ›› 2019, Vol. 50 ›› Issue (4): 512-516.doi: 10.16098/j.issn.0529-1356.2019.04.018

• 组织学胚胎学发育生物学 • 上一篇    下一篇

血管紧张素(1-7)通过抑制中电导钙激活钾离子通道蛋白表达参与肾脏纤维化

许石 刘耀浩 王丽萍*   

  1. 1.华北理工大学基础医学院解剖学系; 2.华北理工大学基础医学院，河北省慢性疾病重点实验室，唐山市慢性病临床基础研究重点实验室，河北 唐山 63210
  • 收稿日期:2018-08-28 修回日期:2018-11-19 出版日期:2019-08-06 发布日期:2019-08-06
  • 通讯作者: 王丽萍 E-mail:mywlpzjm@163.com
  • 基金资助:
    ACE2-Ang (1-7)-Mas调控TLR4-KCa3.1抑制心肌纤维化炎症反应研究;TLR4-KCa3.1在Ang II诱导心肌纤维化炎症反应中的作用研究

Angiotensin （1-7） participating in renal fibrosis by inhibiting intermediate conductance Ca2+ -activated K+ channels protein expression

 XU Shi LIU Yao-hao WANG Li-ping*   

  1. 1.Department of Anatomy, School of Basic Medicine; 2.Hebei Key Laboratory for Chronic Diseases，Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Hebei Tangshan 063210, China
  • Received:2018-08-28 Revised:2018-11-19 Online:2019-08-06 Published:2019-08-06
  • Contact: WANG Li-ping E-mail:mywlpzjm@163.com

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摘要：

目的 探讨血管紧张素（Ang）（1-7）在肾纤维化过程中的保护作用与中电导钙激活钾离子通道（KCa3.1）的关系。 方法 60只雄性小鼠随机分为5组：对照组 (WT)；血管紧张素Ⅱ（Ang Ⅱ）组：皮下注射 Ang Ⅱ ［1.4 mg/(kg.d)］；注射Ang Ⅱ 的同时给予以下药物干预： Ang Ⅱ阻断剂 洛沙坦（Losartan）组：皮下注射 Losartan［40 mg/(kg.d)］； Ang（1-7）组：皮下注射 Ang（1-7）［0.14 mg/(kg.d)］；血管紧张素转化酶2（ACE2）激动剂重氮氨苯脒乙酰甘氨酸盐（DIZE）组：皮下注射DIZE［10 mg/(kg.d)］。连续给药4周后对相关指标进行检测。Masson染色法检测肾组织胶原沉积变化；Western blotting法检测肾组织 Ⅰ 型胶原、Ⅲ 型胶原和 KCa3.1通道蛋白表达的变化。 结果 与对照组相比，Ang Ⅱ组小鼠肾组织内胶原沉积量明显增加（n=12，P<0.01），表明肾纤维化模型复制成功。Ang Ⅱ使肾组织Ⅰ、Ⅲ型胶原合成显著增多（n=6，P<0.01），同时促进了肾组织KCa3.1通道蛋白的表达（P<0.01），而Ang （1-7）及ACE2激活剂 DIZE 的应用抑制了肾组织内胶原沉积量、Ⅰ/Ⅲ型胶原合成及KCa3.1通道蛋白的表达（n=12或6，P<0.01）。结论 Ang （1-7）在肾纤维化过程中发挥保护作用，这一作用可能与其下调肾组织中KCa3.1通道蛋白表达有关。

关键词: 纤维化, 肾脏, 血管紧张素（1-7）, 中电导钙激活钾离子通道蛋白, 免疫印迹法, 小鼠

Abstract:

Objective To investigate the relationship between the protective effect of angiotensin (Ang) （1-7） and the protein expression of intermediate conductance Ca2+ -activated K+ channels (KCa3.1) in renal fibrosis. Methods Totally 60 male mice were randomly divided into 5 groups: control group (WT); Ang Ⅱ group: mice received Ang Ⅱ ［1.4 mg/(kg.d)］by hypodermic injection; Ang Ⅱ blocker group (Losartan): mice received Ang Ⅱ ［1.4 mg/(kg.d)］and Losartan ［40 mg/(kg.d)］by hypodermic injection; Ang （1-7） group: mice received Ang Ⅱ ［1.4 mg/(kg.d)］and Ang （1-7） ［0.14 mg/(kg.d)］by hypodermic injection; diminazene aceturate(DIZE) group: mice received Ang Ⅱ ［1.4 mg/(kg.d)］and DIZE ［10 mg/(kg.d)］by hypodermic injection. After 4 weeks of continuous administration, the related indicators were detected. Masson staining was used to detect the collagen content, and Western blotting was used to detect the protein expression of collagen type Ⅰ, collagen type Ⅲ and KCa3.1 channel. Results Collagen deposition in renal tissue increased significantly after 4 weeks of hypodermic injection of Ang Ⅱ (n=12，P<0.01) compared with the WT group, which suggested that the model of renal fibrosis was successfully reproduced. Ang Ⅱ significantly increased the synthesis of collagen type Ⅰ and Ⅲ (n=6,P<0.01) and increased the expression of KCa3.1 channel protein (n=6，P<0.01) in renal tissues, while Ang （1-7） and ACE2 activator DIZE significantly inhibited those exchanges (n=12 or 6，P<0.01). Conclusion Ang （1-7） plays a protective role in the process of renal fibrosis, which may be related to the downregulation of KCa3.1 channel protein expression in renal tissue.

Key words: Fibrosis, Renal, Angiotensin （1-7）, Intermediate conductance Ca2+ activated K+ channel, Western blotting, Mouse