缬沙坦对野百合碱诱导肺动脉高压模型大鼠肺动脉重构的影响

Effects of Valsartan on pulmonary arterial remodeling in rats with pulmonary hypertension induced by monocrotaline

目的:观察缬沙坦(valsartan)对野百合碱(monocrotaline)所致肺动脉高压大鼠肺血管重构的影响。方法:将健康雄性Wistar大鼠随机分为3组:M组(肺动脉高压模型组)一次性项背部注射野百合碱(60mg/kg)后自由摄食、饮水;V组(缬沙坦干预组),同M组注射野百合碱并同等条件饲养,4周后开始用缬沙坦20mg/(kg·d)灌胃,持续4周达实验终点;C组(正常对照组)一次性项背部注射等量生理盐水后与实验组同等条件饲养。然后经微导管介入测定大鼠肺动脉平均压(mPAP);计算右室肥大指数[RV/(LV+S)];分别采用HE染色、弹力纤维染色及VG染色观察肺动脉结构的改变,计算肺动脉管壁厚度和管腔面积,评价缬沙坦对肺动脉重构的影响。结果:缬沙坦可有效降低野百合碱所致肺动脉高压大鼠模型肺动脉管壁的厚度,增大管腔面积(P<0.01)。结论:缬沙坦可有效抑制肺动脉高压大鼠肺动脉重构,作用机制可能与其抑制AngⅡ介导的增殖效应有关。

Objective To explore the effects of valsartan on pulmonary arterial remodeling in rats with pulmonary hypertension induced by monocrotaline. Methods The healthy male Wistar rats were randomly divided into 3 groups： M group （model of pulmonary hypertension）, were given a single subcutaneous injection of monocrotaline （60 mg/kg） at the back, then free feeding and drinking; Valsartan group were injected with monocrotaline as group M and kept feeding under the same conditions, after 4 weeks with valsartan （20 mg/kg·d） orally for 4 weeks up to the end of the experiment ; control group （group C ） were injected with equivalent saline at the back and kept feeding under the same conditions. Then mean pulmonary artery pressure （mPAP） of the rats was measured by the micro-catheter; the index of the right ventricular hypertrophy was calculated [RV/ （LV ＋ S）]; with HE staining, elastic fiber staining and VG staining to observe pulmonary artery structural changes, calculate the pulmonary artery wall thickness and lumen area and evaluate valsartan on pulmonary artery remodeling. Results Valsartan can reduce the wall thickness and enlarge the wall area of pulmonary arterial in rats with the injection of monocrotaline （P 〈 0.01 ）. Conclusion Valsartan can inhibit the pulmonary arterial remodeling in rats with pulmonary hypertension, the mechanism maybe related to the inhibition of proliferation meditated by angiotensin Ⅱ.