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)一侧颈动脉外膜去除后血管内膜增生的影响。方法13周龄雄性SHR24只去除右侧颈动脉外膜后,随机分为3组(每组8只):SHR对照组、Ang(1～7)组(25μg/kg.h)和Ang(1～7)拮抗剂(Ang779)组(25μg/kg.h);8只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)。机械和化学方法去除大鼠右侧颈动脉外膜,左侧作假手术对照。采用微渗泵植入技术经颈静脉给药2周,鼠尾袖法测量尾动脉收缩压(SBP),放免法测定血浆及双侧颈动脉血管紧张素Ⅱ(AngⅡ)浓度。取双侧颈动脉制成光镜标本,病理图像分析系统测定颈动脉管腔横截面积(LA)、内弹力层围绕面积(IELA)、外弹力层围绕面积(EELA),评价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Ⅱ1型受体(AT1R)蛋白、蛋白激酶C-ζ(PKC-ζ)和胞外信号调节激酶1/2(ERK1/2)蛋白表达。结果Ang(1～7)明显降低SBP(P<0.01),与SHR对照组和Ang779组去外膜侧颈动脉内膜增生比较,Ang(1～7)明显改善因去外膜后引起的血管内膜增殖(P<0.01)。虽然Ang(1～7)未能减少去外膜后颈动脉壁的AngⅡ浓度,但能明显降低颈动脉AT1R蛋白表达(P<0.01)和减少因去外膜后引起的管壁PKC-ζ及ERK1/2蛋白表达(P<0.01)。结论Ang(1～7)可显著抑制SHR去外膜后颈动脉的内膜增生,这一作用可能是其通过下调颈动脉ATR和减少PKC-ζ及ERK1/2蛋白表达而实现的。
Objective To investigate the effect of angiotensin-（1-7） on intimal hyperplasia in carotid artery 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）, Ang 779 and SHR control group. Eight Wistar-Kyoto rats were selected as normal control group （WKY group）. Adventitia in fight carotid artery was removed mechanically and chemically. Adventitia in left carotid artery was left intact. Ang-（1-7） in saline 25 μg/（kg·h） was infused intravenously for 14 days. The systolic blood pressure （SBP） was measured with tail-cuff method. Plasma and carotid artery angiotensin Ⅱ（Ang Ⅱ） levels were determined by radioimmunoassay. Lumen cross section area （LA）, intraelastic layer area （IELA） and extraelastic layer area （EELA） were measured by computed video processing, and the ratio of （IELA-LA）/（EELA-IELA） calculated. The expression of local angiotensin Ⅱ type 1 receptor （AT1 R）, protein kinase C-ζ（PKC-ζ） and extracellular signal-regulated kinase1/2（ERK1/2） protein in both arteries was determined by immunohistochemistry method. Results Ang-（1-7） significantly decrease SBP（P〈0.01）. Ang-（1-7） markedly inhibited the intimal hyperplasia after adventitia removal compared with SHR control and Ang 779 group（ P〈0. 01）. Although Ang-（1- 7） had no significant effect on plasma and local Ang Ⅱ levels （P〉0.05）, the expression of AT1R, PKC-ζ and ERK1/2 protein in Ang-（1-7） group was significantly down-regulated compared with Ang 779 and SHR group （all P〈0.01 ）. Conclusion Ang-（ 1- 7） effectively reduce SBP and improve markedly intimal hyperplasia caused by advential removal in SHR , which was associated with the down - regulation of local AT1 R , PKC - ζ and ERK1/2 protein.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2007年第9期741-747,共7页
Chinese Journal of Hypertension
