解剖学报

解剖学报 ›› 2014, Vol. 45 ›› Issue (3): 411-415.doi: 10.3969/j.issn.0529-1356.2014.03.021

• 组织学胚胎学发育生物学 • 上一篇    下一篇

血管紧张素II通过下调血管外膜过氧化氢酶表达促进成纤维细胞表型转化

沈凯1 林卓明2,3 陈士良1 袁国裕1 刘晓光2*   

  1. 1. 舟山医院心血管内科，浙江  舟山 316000;2. 温州医科大学附属舟山医院细胞分子生物学实验室，浙江 舟山 316000; 3. 舟山市普陀区人民医院检验科，浙江 舟山 316000
  • 收稿日期:2013-09-23 修回日期:2013-12-06 出版日期:2014-06-06 发布日期:2014-06-06
  • 通讯作者: 刘晓光 E-mail:lxg2004@foxmail.com
  • 基金资助:

    浙江省医药卫生科技计划资助项目

Angiotensin Ⅱ promotes fibroblasts phenotypic transformation through down-regulating adventitial catalase expression

SHEN Kai1 LIN Zhuo-ming 2,3 CHEN Shi-liang1 YUAN Guo-yu1 LIU Xiao-guang 2*   

  1. 1.Department of Cardiology,Zhoushan Hospital, Zhejiang Zhoushan 316000,China; 2.Cell and Molecular Laboratory, Zhoushan Hospital Affiliated to Wenzhou Medical University, Zhejiang Zhoushan 316000, China; 3.Department of Clinical Laboratory, Putuo Hospital in Zhejiang Province, Zhejiang Zhoushan 316000, China
  • Received:2013-09-23 Revised:2013-12-06 Online:2014-06-06 Published:2014-06-06
  • Contact: LIU Xiao-guang E-mail:lxg2004@foxmail.com

摘要：

目的 探讨血管紧张素Ⅱ(AngⅡ)与血管成纤维细胞（VAF）表型转化的关系。方法 利用AngⅡ微泵灌注制备高血压大鼠模型，共18只随机分为未处理组﹑生理盐水对照组﹑AngⅡ灌注组，每组6只。分别检测各组大鼠尾动脉收缩压及血管形态学改变，免疫组织化学检测各组大鼠颈动脉血管过氧化氢酶(CAT) 及氧化应激产物4-羟烯酸(4HNE)蛋白的表达，采用Western blotting技术检测外膜成纤维CAT蛋白在不同AngⅡ孵育时间和浓度下的表达。 结果 与未处理组和生理盐水对照组相比，大鼠颈动脉HE染色和收缩压检测结果显示，AngⅡ灌注组大鼠颈动脉中膜厚度和收缩压明显增加(P<0.01)，动脉形态结构有明显改变，且有显著的病理性血管重塑发生；与未处理组比较，免疫组织化学检测显示AngⅡ灌注组大鼠颈动脉血管抗氧化氢酶表达显著降低(P<0.05)，而氧化应激产物4HNE表达显著增加(P<0.05)，Western blotting检测显示，随着AngⅡ浓度增高和孵育时间延长均能诱导CAT表达下调。 结论 AngⅡ能够通过下调血管外膜CAT的表达进而促进血管外膜细胞表型转化，导致动脉的病理性血管重塑。

关键词: 血管紧张素Ⅱ, 过氧化氢酶, 表型, 转化, 成纤维细胞, 免疫印迹法, 大鼠

Abstract:

Objective To investigate the relationship between angiotensin Ⅱ (AngⅡ) and transformation of vascular fibroblasts phenotype.Methods Eighteen rats were randomly assigned into the untreated group, mini-pump infusion of saline group and mini-pump infusion of AngⅡ group which was used as the hypertension model. Their systolic pressure and vascular morphology were examined. The expression of catalase (CAT) and 4HNE was examined by immunohistochemistry. Western blotting was used to examine the expression of CAT of adventitial fibroblasts which were cultured by different incubation times and concentrations of AngⅡ. Results Compared with untreated and mini-pump infusion of saline groups, the systolic pressure and carotid media thickness stained by HE of mini-pump infusion of AngⅡ group were significantly higher(P<0.01).The results of immunohistochemistry showed that the expression of CAT ofAngⅡ group was significantly lower than that of untreated group , however the expression of 4HNE of AngⅡ groupwas higher than that of untreated group (P<0.05). Furthermore, the results of Western blotting indicated that the effect of Ang Ⅱ on down-regulation of CAT function was in a dose and incubation time dependent manner. Conclusion AngⅡ down-regulates adventitial CAT expression and promotes fibroblasts phenotypic transformation which leads to pathological arterial vascular remodeling.

Key words: Angiotensin Ⅱ, Catalase, Phenotype, Transformation, Fibroblast, Western blotting, Rat