雷米普利通过调节细胞外调节激酶1/2的活性抑制肺动脉高压大鼠肺血管重构

目的探讨雷米普利抑制野百合碱（MCT）诱导的肺动脉高压（PAH）大鼠肺血管重构是否与调节细胞外调节激酶1/2（ERK1/2）活性有关。方法雄性Sprague-Dawley大鼠30只,质量280～320g,随机分为：正常对照组、PAH组、PAH＋雷米普利组。PAH组和PAH＋雷米普利组一次性颈部注射MCT60mg/kg后,PAH＋雷米普利组用雷米普利灌胃,PAH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。4周后,测定大鼠的右室收缩压（RVSP）和右心室肥厚指数（RVHI）,并用图像分析软件,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,%）。放射免疫法检测肺组织中血管紧张素Ⅱ（AngⅡ）浓度。Western免疫印迹分析肺组织中ERK1/2磷酸化水平。结果PAH组的RVSP、RVHI、WT（%）、WA（%）、肺组织AngⅡ浓度和ERK1/2磷酸化水平均显著高于正常对照组;雷米普利组RVSP、RVHI、WT（%）、WA（%）、肺组织AngⅡ浓度和ERK1/2磷酸化水平均明显低于PAH组。结论雷米普利抑制MCT诱导的肺血管重构的机制可能与降低肺组织ERK1/2磷酸化水平有关。

Ramipril Inhibits Pulmonary Vascular Remodeling by Regulating ERK 1/2 Activation in Rats with Pulmonary Arterial Hypertension

Objective To investigate whether or not that Ramipril by regulating extracellular regulated protein kinases 1/2, （ ERK 1/2） ] activation inhibited pulmonary vascular remodeling in the model of pulmonary arterial hypertension induced by monocrotaline（MCT） in rats. Methods 30 Sprague- Dawley rats were randomly di- vided into three groups： normal control group, pulmonary arterial hypertension（PAH） group and PAH ＋ Ramipfil treatment group. The rats in two latter groups were injected 60mg/kg of MCT subcutaneously and then received normal drinking water or Ramipril in drinking water. The rats in normal control group were injected normal saline subcutaneously first and then received normal drinking water. After 4 weeks of treatment, fight 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. AngioteminⅡ（AngⅡ） concen- tration in lung was measured by radioimmunoassay. ERK 1/2 was analysed by Western blotting. Results After four weeks, those parameters of RVSP, RVHI, WT % and WA %, pulmonary AngⅡ concentration and the level of phosphorylation of ERK 1/2 in PAH group were significantly increased compared with control group. However, the above parameters were dramatically decreased in Ramipril treatment group. Conclusion Ramipril can prevent the development of pulmonary hypertension induced by monocrotaline and inhibit pulmonary vascular remodeling, which are associated with down-regulating the level of phosphorylation of ERK 1/2.