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中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (12): 1389-1394.

• 研究原著 • 上一篇    下一篇

血管紧张素-(1-7) 对自发性高血压大鼠去外膜颈动脉血管结构和功能的影响

王安才, 李俊, 曹蘅, 汪俊元, 曹晓霞, 吴明   

  1. 皖南医学院弋矶山医院心血管内科, 芜湖 241001, 安徽
  • 收稿日期:2006-08-04 修回日期:2006-11-13 出版日期:2006-12-26 发布日期:2020-11-06
  • 作者简介:王安才, 男, 医学博士, 主任医师, 教授, 硕士研究生导师, 研究方向:高血压病的预防和治疗。Tel:13909633699 E-mail:yjswac@sina.com

Effect of angiotensin-(1-7) on intimal hyperplasia and blood flow in carotid artery after adventitia removal in spontaneously hypertensive rats

WANG An-cai, LI Jun, CAO Heng, WANG Jun-yuan, CAO Xiao-xia, WU Ming   

  1. Department of Cardiology, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China
  • Received:2006-08-04 Revised:2006-11-13 Online:2006-12-26 Published:2020-11-06

摘要: 目的 研究血管紧张素-(1-7) [ Ang-(1-7) ] 对自发性高血压大鼠(SHR) 一侧颈动脉去外膜血管结构和功能的影响。方法 24 只SHR 去除右侧颈动脉外膜后, 随机分为3 组(每组8 只):SHR 组、Ang-(1-7) 组和Ang779 [ Ang-(1-7) 拮抗剂] 组;8 只WKY 鼠作为对照组(WKY 组) 。去除大鼠右侧颈动脉外膜,左侧作假手术对照。颈静脉给药2 周, 测量尾动脉收缩压(SBP) 、双侧颈动脉血流量和血浆及双侧颈动脉血管紧张素Ⅱ(Ang Ⅱ) 浓度。取双侧颈动脉制成光镜标本, 病理图象分析系统测定颈动脉内膜和中膜增生状况。免疫组织化学方法测定双侧颈动脉血管紧张素1(AT1) 受体蛋白表达。TUNEL 法检测血管组织细胞凋亡。结果 Ang-(1-7) 组SBP较Ang779 组和SHR 组显著下降(P<0.01) 。Ang-(1-7) 组未去外膜侧和去外膜侧内膜增生较SHR 组和Ang779 组明显改善(P<0.01) 。Ang-(1-7) 组去外膜侧颈动脉血流量显著高于SHR 组和Ang779 组(P<0.01) 。去外膜侧颈动脉Ang Ⅱ浓度显著高于未去外膜侧(P<0.01) 。SHR 组和Ang779 组去外膜侧颈动脉AT1受体蛋白表达显著高于未去外膜侧(P<0.01),Ang-(1-7) 组未去外膜侧和去外膜侧颈动脉AT1受体蛋白表达明显低于SHR 组和Ang779 组(P<0.01) 。Ang-(1-7) 组未去外膜侧和去外膜侧凋亡指数较SHR 组和Ang779 组显著升高(P<0.01) 。结论 Ang-(1-7) 能降低SHR 的收缩压和血管阻力,增加去外膜侧颈动脉血流量, 抑制去外膜后颈动脉内膜增生。这一作用可能与Ang-(1-7) 下调颈动脉AT1 受体, 促进血管组织细胞凋亡有关。

关键词: 血管紧张素-(1-7), 大鼠, 外膜, 血管紧张素Ⅱ型受体, 细胞凋亡

Abstract: AIM: To investigate the effect of angiotensin-(1-7) on intimal hyperplasia and blood flow in carotidartery after adventitia removal in SHR.METHODS: Twenty-four spontaneously hypertensive rats(SHR) with right carotid artery adventitia removed were randomly divided into 3 groups (n =8, each):Ang-(1-7), Ang779 and SHR control group.Eight Wistar-Kyoto rats were selected as normal control grouP(WKY group).Adventitia in right carotid artery was removed by mechanical and chemical means.Adventitia in left carotid artery was sham-operated. Ang-(1-7) in saline (25μg·kg-1·h-1) was infused intravenously for 14 days.The systolic blood pressure (SBP) was taken.The velocity of carotid artery was detected by electromagnetic rheometer.Plasma and carotid artery angiotensin II (Ang Ⅱ)levels were measured by radioimmunoassay.The intimal hyperplasia was measured by computed video processing.The expression of local angiotensin II type 1 receptor(AT1R) protein in both arteries was determined by immunohistochemistry method.The apoptosis of vascular tissue cell in carotid artery was evaluated by terminal deoxynucleotidyl transferase-mediated DutPnick-end labeling(TUNEL) assay and measured by image analyse system.RESULTS: SBPin Ang-(1-7) grouPwas significantly lower than that in Ang779 and SHR grouP(all P<0.01).Compared with Ang779 and SHR group, the carotid blood flow in no adventitia removal in Ang-(1-7)grouPwas increased significantly (P<0.01).Compared with no adventitia removal, the intimal hyperplasia in adventitia removal was exacerbated significantly (P<0.05), and it was markedly inhibited in Ang-(1-7)grouP(P<0.01).Carotid artery Ang Ⅱlevel in adventitia removal was significantly higher than that in no adventitia removal (P<0.01).Ang-(1-7) had no significantly effect on plasma and local Ang Ⅱlevels (P>0.05).The expression of AT1R protein in adventitia removal was significantly higher than that in no adventitia removal in SHR and Ang779 group.Compared with Ang779 and SHR group, the expression of AT1R protein in Ang-(1-7) grouPwas down-regulated significantly (all P<0.01).Compared with Ang779 and SHR group, apoptotic index in adventitia removal and no adventitia removal in Ang-(1-7) grouPwas increased significantly (all P<0.01).CONCLUSION: Ang-(1-7) can significantly improve intimal hyperplasia and increase blood flow in carotid artery with adventitia removal in SHR, which may be related to the down-regulation of local AT1 R protein.

Key words: angiotensin-(1-7), rats, carotid artery, adventitia, angiotensin II type 1 receptor, apoptosis

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