黄芪皂苷甲对高血压大鼠离体血管舒张功能及一氧化氮的影响

Effect of astragaloside Ⅳ on relaxation and molecule mechanism in isolated rat 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舒张功能异常,及血管一氧化氮(NO)含量和一氧化氮合酶Ⅲ型(eNOS)蛋白表达的影响。方法2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(3.3 mg·kg^(-1))、模型组、AsⅣ低剂量组(0.33 mg·kg^(-1))、AsⅣ中剂量组(1.0 mg·kg^(-1))和AsⅣ高剂量组(3.3 mg·kg^(-1))。左前肢动脉测压法动态观察大鼠血压变化,测定心脏和血管形态学指标,离体血管环张力测定法检测大鼠胸主动脉对NO介导的内皮功能反应性,ELISA法测定大鼠血浆和血管组织硝酸盐和亚硝酸盐含量,Western blotting测定胸主动脉组织eNOS蛋白表达。结果低剂量AsⅣ仅降低血管重量指数,中剂量AsⅣ可降低血压和左室重量指数(LVMI),高剂量AsⅣ在降压的同时,可降低心脏重量指数、LVMI和血管重量指数。AsⅣ可改善NO介导的内皮依赖性舒张作用,明显升高血管组织NO含量,并能使血管组织eNOS的蛋白表达恢复到正常水平。结论AsⅣ能降低血压,逆转压力过载引起的血管肥厚和血管内皮舒张功能失调,其作用与其上调eNOS蛋白表达、升高胸主动脉组织NO含量有关。

AIM To investigate the effects of long-term treatment with astragaloside （As） Ⅳ on blood pressure and vascular relaxation dysfunction in hypertensive model induced by aortic banding from adult rats. METHODS Hypertensive rat model was induced by aortic banding. Twelve weeks after surgery, the 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. Blood pressure was measured by the modified tail-cuff method once every four weeks. At the end of the 12-week treatment period, heart mass index （HMI） and left ventrical mass index （LVMI） were measured. Vascular hypertrophy was assessed by determination of standardized aortic weight. The relaxation effect of As Ⅳ on thoracic aortic rings isolated from hypertensive rats induced by aortic banding was recorded. Plasma and aortic nitrite/nitrate levels were determined by ELISA, and protein expression of eNOS was determined by western blotting. RESULTS The increasing systolic blood pressure of the rats with aortic banding was significantly reduced by As Ⅳ at the dose of 1.0 and 3.3 mg.kg^-1, respectively. LVMI, HMI and standardized aortic weight were increased in the rats with aortic banding, and were attenuated by treatment with 3.3 mg.kg^-1 As Ⅳ. In the hypertensive rats, endothelium-dependent relaxation to ACh were markedly blunted as compared with sham-operated rats, and were improved by the administration of As Ⅳ with concentration dependent. Moreover, aortic nitrite/nitrate and eNOS protein levels were reduced in the hypertensive rats. As Ⅳ attenuated the reduction of aortic nitrite/nitrate and eNOS protein levels. CONCLUSIONS Long-term treatment with As Ⅳ could reduce blood pressure, regress vascular hypertrophy, and attenuate endothelial dysfunction in the aortic-banding rats, which is partly resulted from up-regulating protein expression of aortic eNOS and elevating nitrite/nitrate level.