雷米普利对肺动脉高压大鼠血管紧张素-（1-7）浓度的影响

Effects of ramipril on Ang-（1-7） concentration in pulmonary arterial hypertension rat

目的 探讨雷米普利对野百合碱（MCT）诱导的肺动脉高压大鼠血浆中血管紧张素-（1-7）[Ang-（1-7）]浓度的影响.方法 雄性SD大鼠60只,随机分为对照组、MCT组和雷米普利组.MCT组和雷米普利组一次性颈部注射MCT 60 mg/kg后,雷米普利组给予雷米普利灌胃,MCT组用生理盐水灌胃.对照组颈部注射生理盐水后,用生理盐水灌胃.三组大鼠给予雷米普利或生理盐水2周和4周后,测定大鼠的右室收缩压（RVSP）和心室重量变化,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%）.采用酶联免疫分析（ELISA）检测各组大鼠血浆中Ang-（1-7）的浓度.结果 野百合碱诱导2周后,MCT组与对照组相比,RVSP、各心室的重量无明显变化,WT%、WA%以及Ang-（1-7）的浓度显著升高;野百合碱诱导四周后,MCT组与对照组相比,RVSP、各心室的重量、WT%、WA%和Ang-（1-7）的浓度显著升高.野百合碱诱导2周和4周后,雷米普利组与MCT组相比,Ang-（1-7）的浓度显著升高,其他指标与对照组相比无明显的差异.结论 对野百合碱诱导的肺动脉高压模型,雷米普利可预防肺动脉高压的发生,其机制可能与升高血浆中Ang-（1-7）浓度有关.

Objective To investigate effects of Ramipril on Ang-（1-7） concentration in plasma in rat model of pulmonary arterial hypertension induced by monocrotaline （MCT）. Methods Sixty Sprague-Dawley rats were randomly divided into three groups： control group,MCT group and Ramipril group. The rats in two latter groups were injected 60 mg/kg of MCT subcutaneously and then received normal drink water or Ramipril in drink water. The rats in control group were injected normal saline subcutaneously first and then received normal drink water. After two and four 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. Ang-（1-7） concentration in plasma were measured. Results Two weeks after monocrotaline injection, no significant difference was found between MCT and control group in RVSP and RVHI. Compared with control group, WT%, WA % and Ang-（1-7） concentration were significantly increased in MCT group. Four weeks after injection, compared with control group, RVSP, RVHI, WT%, WA% and Ang-（1- 7） concentration were significantly increased in MCT group. However, two and four weeks after injection, com pared with MCT group, Ang-（1-7） concentration were significantly increased in Ramipril group. No significant difference was found between Ramipril group and control group among the other parameters. Conclusion Ramipril can prevent the development of pulmonary hypertension induced by monocrotaline, which are associated with upregulation Ang-（1-7） concentration.