罗格列酮对血管紧张素Ⅱ诱导高血压大鼠的血压影响及其机制

Effect of rosiglitazone on angiotensin Ⅱ-induced hypertension and its mechanism in rats

目的:探讨罗格列酮(RSG)对血管紧张素Ⅱ(AngⅡ)诱导高血压大鼠血压的影响及机制。方法:选择24只SD大鼠随机分为4组:正常对照组、RSG组、AngⅡ组及AngⅡ+RSG组。每组6只大鼠(n=6)。采用alzet渗透泵持续皮下泵入AngⅡ[300 ng/(kg·min)×7 d]建立高血压大鼠模型,RSG组和AngⅡ+RSG组给予RSG灌胃[5 mg/(kg·d)]7 d,7 d后观察各组大鼠的血压、心脏质量指数、空腹血糖变化,测定大鼠主动脉NADPH氧化酶的活性及超氧阴离子的含量。结果:与AngⅡ组对比,AngⅡ+RSG组血压下降[(136±6)mm Hg vs.(166±6)mmHg,P<0.01]及心脏质量指数下降[(3.54±0.04)mg/kg vs.(3.85±0.08)mg/kg,P<0.01];NADPH氧化酶活性及血管超氧阴离子含量下降[(288.49±36.19)cpm/μg vs.(584.04±69.67)cpm/μg,P<0.01;(2 792.82.7±726.76)cpm/mg vs.(4 765.50±597.34)cpm/mg,P<0.01]。结论:RSG抑制NADPH氧化酶的活性,降低血管超氧阴离子的含量,拮抗血管AngⅡ诱导的血压升高及心肌肥厚,发挥保护心血管的作用。

AIM： To study the effects of rosiglitazone on angiotensin Ⅱ （AngⅡ）-induced hypertension in rats and to explore the associated mechanism. METHODS： Twenty-four Sprague Dawley rats were divided equally into four groups ： control group, rosiglitazone group, AngⅡ group, and Ang Ⅱ ＋ rosiglitazone group. Rosiglitazone [ 5 mg/（ kg· d） ] was administrated with AngⅡ [ （300 ng/（ kg. min） s.c., osmotic pump] for 7 days in the rats. Rosiglitazone was also given in sham-operated rats. Blood pressure, heart weight index values, vascular superoxide anion production and NADPH oxidase activity were determined. RESULTS： Compared with those in Ang Ⅱ group, blood pressure, heart weight index values, vascular superoxidase production and NADPH oxidase activity all decreased in AngⅡ ＋ rosiglitazone group [ （ 136 ±6） mmHg vs. （ 166 ±6） mmHg ; （3.54 ±0. 04） mg/g vs. （ 3.85 ±0. 08 ） mg/g; （288.49 ±36. 19） cpm/μg vs. （584. 04 ±69. 67） cpm/μg, respectively, all P 〈0. 01 ]. CONCLUSION： Rosiglitazone prevents the development of hypertension and myocardial hypertrophy by inhibiting NADPH oxidase activity, reducing superoxide anion production and lowering AngⅡ-induced hypertension.