黄芪皂苷甲对高血压大鼠血管肥厚及ET-1诱导离体血管收缩功能的影响

Effects of astragaloside Ⅳ on vascular hypertrophy and vascular contraction in isolated aortic rings from hypertensive rats

目的研究长期给予黄芪皂苷甲(AsⅣ)对高血压大鼠腹主动脉血管肥厚和血管收缩功能异常,以及对血管ET-1含量及其受体蛋白表达的影响。方法两肾间腹主动脉缩窄制备高血压大鼠,随机分为假手术组、AsⅣ假手术组(3.3mg·kg-1)、模型组、As Ⅳ低剂量组(0.33mg·kg-1)、AsⅣ中剂量组(1.0mg·kg-1)和AsⅣ高剂量组(3.3mg·kg-1),形态测量法测定血管形态学指标,离体血管环张力测定法检测大鼠胸主动脉对ET-1的反应性,HE染色法测定血管肥厚程度,ELISA法测定大鼠血浆和血管组织ET-1含量,Western blotting方法测定胸主动脉组织ETA和ETB的蛋白水平。结果AsⅣ高剂量组降低管壁厚度和中层厚度;在离体血管环功能测定实验中,压力过载大鼠胸主动脉在内皮存在时,ET-1诱导的血管收缩反应降低,As Ⅳ可以剂量依赖性的改善上述血管反应并降低血管组织ET-1的含量;各剂量AsⅣ均能下调ETA受体和ETB受体的蛋白表达。结论As Ⅳ逆转压力过载引起的血管肥厚,改善血管对ET-1诱导的血管收缩反应性,其作用与其下调ETA受体和ETB受体蛋白水平,使胸主动脉组织ET-1含量下降有关。

AIM To investigate the effects of long-term treatment with astragaloside （As） Ⅳ on vascular hypertrophy and vascular contraction in hypertensive model induced by aortic banding. METHODS Hypertensive rat model was induced by aortic banding. Twelve weeks after surgery, rats with or without aortic banding were randomized into six groups： sham, sham ＋ As Ⅳ 3.3 mg·kg^-1, model, model ＋ As Ⅳ 0.33 mg·kg^-1, model ＋ As Ⅳ 1.0 mg·kg^-1, model ＋ As Ⅳ 3.3 mg·kg^-1. At the end of the 12-week treatment period, vascular hypertrophy was assessed by HE staining. The effect of As Ⅳ on the contraction of thoracic aortic rings isolated from the hypertensive rats was recorded. Plasma and aortic ET-1 levels were determined by ELISA, and vascular tissue ETA and ETB protein contents were determined by western blotting. RESULTS Aortic wall thickness and media thickness were increased in rats with aortic banding. Treatment with 3.3 mg·kg^-1As Ⅳ reduced these increased parameters to the levels similar to the sham-operated rats. In the hypertensive rats, endothelium- dependent contraction to ET-1 were markedly blunted as compared with the sham-operated rats, and were improved by As Ⅳ with concentration dependent. Moreover, aortic tissue ET-1 level was reduced in the hypertensive rats by As Ⅳ. As Ⅳ down-regulated the elevated protein expression of tissue ETA and ETB in the hypertensive rats. CONCLUSION Long-term treatment with As Ⅳ could regress vascular hypertrophy and attenuate endothelium-dependent contraction-dysfunction in aortic-banding rats, which is partly resulted from attenuating aortic ETA and ETB protein expression and reducing ET-1 level.