摘要
【目的】探讨血管紧张素-(1-7)[Ang-(1-7)]对野百合碱(MCT)诱导的肺动脉高压的作用及相关机制。【方法】雄性Sprague-Dawley大鼠80只随机分为:正常对照组(control)、MCT组、MCT+Ang-(1-7)组、control+Ang-(1-7)组。MCT组和MCT+Ang-(1-7)组颈静脉注射MCT60mg/kg,24h后经微泵持续泵入生理盐水或Ang-(1-7)(24μg·kg-1·h-1)。control和control+Ang-(1-7)组颈部注射生理盐水,24h后经微泵泵入生理盐水或Ang-(1-7)(24μg·kg-1·h-1)。治疗4周后测定大鼠的右室收缩压(RVSP)和右心室肥厚指数(RVHI),测定肺小动脉管壁厚度(WT)占动脉外径(ED)的百分比(WT%)及管壁面积(WA)占血管总面积的百分比(WA%)。通过放射免疫方法检测血浆及肺组织中血管紧张素Ⅱ(AngⅡ)浓度。Western blot分析肺组织中细胞外调节蛋白激酶1/2(ERK1/2)磷酸化水平。【结果】与control组相比,MCT组RVSP、RVHI、WT%、WA%、肺组织AngⅡ浓度、ERK1/2磷酸化水平显著升高(P<0.01);MCT+Ang-(1-7)组与MCT组相比,RVSP、RVHI、WT%、WA%、ERK1/2磷酸化水平均明显降低(P<0.01);control组、control+Ang-(1-7)组、MCT+Ang-(1-7)组三组间RVSP、RVHI、WT%、WA%、ERK1/2磷酸化水平差异无显著性意义(P>0.05)。【结论】在MCT诱导的肺动脉高压模型中,Ang-(1-7)可能通过降低ERK1/2磷酸化水平,抑制肺血管的重构,预防肺动脉高压的发生。
[Objective] To investigate the effect and mechanism of Ang-（1-7） on pulmonary arterial hypertension induced by MCT. [ Methods] Eighty Sprague-Dawley rats were randomly divided into four groups： control group, MCT group, MCT ＋ Ang-（1- 7） group, and control ＋ Ang-（1-7） group. Twenty-four hours after injection of MCT, the rats in MCT ＋ Ang-（1-7） group and MCT group were allocated to intravenous infusion of either Ang-（1-7） （24 μg·kg-1·h-1） or saline by osmotic minipumps. Twenty- four hours after injection of saline, rats in control ＋ Ang-（1-7） group and control group were allocated to intravenous infusion of either Ang-（1-7） （24 μg·kg-1·h-1） or saline by osmotic minipumps. After 4 weeks of treatment, right ventricular systolic pressure （RVSP） and right ventricular hypertrophy index （RVHI） were measured. Percentage of wall thickness （WT%） and percentage of wall area （WA%） of pulmonary arterioles were evaluated. Angiotensin Ⅱ （Ang Ⅱ ） concentration in plasma and lung were measured by radioimmunoassay. ERK1/2 activation was analyzed by Western blotting. [Results] After four weeks, these parameters of RVSP, RVHI, WT%, WA%, pulmonary Ang Ⅱ concentration and the level of phosphorylation of ERK1/2 in MCT group were significantly increased compared with control group （P 〈 0.01）. The parameters of RVSP, RVHI, WT%, WA%, and the level of phosphorylation of ERK1/2 in MCT ＋ Ang-（1-7） group were significantly decreased compared with MCT group （P 〈 0.01）. There were no significant difference concerned RVSP, RVHI, WT%, WA%, and the level of phosphorylation of ERK1/2 among control group, MCT ＋ Ang-（1-7） group, and control ＋ Ang-（1-7） group （P 〉 0.05）. [Conclusion] Down-regulation of the level of phosphorylation of ERK1/2, Ang-（1-7） can inhibit pulmonary vascular remodeling and prevent the development of pulmonary arterial hypertension.
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2009年第3期264-268,共5页
Journal of Sun Yat-Sen University:Medical Sciences
基金
广东省自然科学基金(04300348)
