血管紧张素-(1-7)对自发性高血压大鼠去外膜颈动脉血管功能的影响

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功能的影响。方法13周龄雄性SHR24只用机械和化学方法去除右侧颈动脉外膜,左侧作假手术对照后,随机分为3组(每组8只),即SHR对照组、Ang-(1-7)组(25μg·kg-1·h-1)和Ang-(1-7)拮抗剂Ang779组(25μg·kg-1·h-1);8只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)。采用微渗泵植入技术经颈静脉给药2周,鼠尾袖法测量给药前后鼠尾动脉收缩压(SBP)。电磁流量计测量双侧颈动脉血流量。放免法测定血浆及双侧颈动脉血管紧张素Ⅱ(AngⅡ)浓度。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)蛋白表达。TUNEL法检测大鼠血管组织细胞凋亡情况。结果Ang-(1-7)组SBP较SHR对照组和Ang779组显著下降(P<0.01)。Ang-(1-7)组去外膜侧颈动脉血流量显著高于SHR对照组和Ang779组(P<0.01)。去外膜侧颈动脉AngⅡ浓度显著高于未去外膜侧(P<0.01)。去外膜侧颈动脉AT1R蛋白表达较未去外膜侧明显增多(P<0.01),而Ang-(1-7)组双侧颈动脉AT1R蛋白表达明显低于SHR对照组和Ang779组(P<0.01)。Ang-(1-7)组去外膜侧和未去外膜侧凋亡指数较SHR对照组和Ang779组显著升高(P<0.01)。结论去除血管外膜后,血管内皮细胞和平滑肌细胞增生,凋亡减少,管腔狭窄,血流量降低,血管功能出现障碍。Ang-(1-7)能通过下调颈动脉AT1R蛋白表达,促进血管组织细胞凋亡,改善血管功能。

The effect of angiotensin-(1-7) on vascular function after carotid artery adventitia removal in spontaneously hypertensive rats

Objective To investigate the effect of angiotensin-（1-7） on vascular function after adventitia removal in spontaneously hypertensive rats（SHR）. Methods Twenty-four male SHR（13w） were randomly divided into 3 groups（ n = 8, each）, all rats underwent right carotid artery adventitia removal and left carotid artery sham operation. The three groups were Ang-（1-7） group, Ang779 group and SHR control group. Additional 8 male rats were enrolled as normal control group （WKY group）. Ang-（1-7） in saline （25 μg·kg^-1 · h^-1 ）was infused intravenously lasted for 14 days. The systolic blood pressure （SBP） was measured with tail cuff method. The velocity of carotid arterywas detected by electromagnetic rheometer. Plasma and carotid artery Ang Ⅱ levels were evaluated with radioimmunoassay. The expression of AT1 R in both carotids was determined by immunohistochemistry. The apoptosis of carotid artery vascular tissue ceils was evaluated by terminal deoxynucleotidyl transferase mediated Dutp nick end labeling （TUNEL） .Results It showed the SBP decreased obviously in Ang-（1-7） group than Ang779 group and control group（ P 〈 0.01）. The carotid blood flow with adventitia removal of Ang-（1-7） group increased significantly compared with Ang779 group and control group （ P 〈 0.01 ）. The concentration of Ang-（1-7） was significantly higher in adventitia removal carotid artery than sham operation artery （ P 〈 0. O1 ）. In the removal side of carotid artery, the expression of AT1R was higher than opposite side, and the expression was obviously lower in Ang- （1-7） group than Ang779 or control group（ P 〈 0.01）. Apoptosis of carotid artery in Ang- （1-7） group was significantly higher than that in Ang779 group and SHR control group（ P 〈 0.01 ）. Conclusion Ang-（1-7） could down regulate the express of AT1 R and inhibit intima hyperplasia in carotid artery after adventitia removal. Ang-（1-7） had protection on structural and functional lesion caused b