摘要
目的研究苯那普利和坎地沙坦单用或联用对自发性高血压大鼠心肌肥厚过程中血流动力学及转化生长因子β1(TGF-β1)表达的影响。方法给予12周龄自发性高血压大鼠苯那普利10 mg/(kg.d)、坎地沙坦4 mg/(kg.d)或半剂量联合治疗,12周后,利用超声心动图检测射血分数,测定血流动力学参数,同时检测左室质量指数和左室后壁厚度,HE染色观察心肌病理学改变,免疫组化和蛋白印迹法测定心肌中TGF-β1蛋白的表达。结果苯那普利和坎地沙坦均可降低LVMI和左室后壁厚度(P<0.01),改善血流动力学参数,降低心肌小动脉中膜面积与管腔面积比值(P<0.01),减少心肌TGF-β1表达(P<0.01),联合应用具有协同作用,且能增加射血分数(P<0.01)。结论苯那普利和坎地沙坦联用对于逆转心肌肥厚,调节心脏血流动力学参数以及心功能具有协同作用,可能与下调TGF-β1的表达有关。
Objective To investigate the effects of benazepril and candesartan on hemodynamics parameters and transforming growth factor β1 （TGF-β1） expression during myocardial hypertrophy in spontaneous hypertensive rats （SHR）. Methods 12-week-old SHRs were treated with benazepril at 10 mg/（kg · d）, candesartan at 4 mg/（ kg · d） and a combination of 2 drugs at half dose, respectively, for 12 weeks. After 12 weeks treatment, ejection fraction（EF） was acquired with the echocardiographic system. Left ventricular catheter was placed via right common carotid artery and hemodynamic parameters were determined. Left ventricular mass index（LVMI） and thickness of left ventricular posterior wall（LVPW） were also examined. Meanwhile, myocardium pathological structures were accessed with HE-staining. Expressions of TGF-β1 were detected using immunohistochemistry and Western blot analysis respectively. Results LVMI, thickness of LVPW, ratio of media area to lumen area in myocardial arteriole, expressions of TGF - β 1 were decreased after the treatment of benazepril or candesartan （P 〈0. 01 ）. Hemodynamic parameters were also improved. After the combined treatment, the synergistic effect could be observed and EF was increased. Conclusion Synergistic attenuation of myocardial hypertrophy and improving of hemodynamic parameters in SHRs are produced by combined use of benazepril and candesartan possibly through negative modulation of TGF-β1 experssion.
出处
《基础医学与临床》
CSCD
北大核心
2011年第2期149-154,共6页
Basic and Clinical Medicine
基金
江苏省教育厅科学研究基金(JH012076)
南通大学校级自然科学研究项目(08Z047)
关键词
心肌肥厚
转化生长因子Β1
苯那普利
坎地沙坦
自发性高血压大鼠
myocardial hypertrophy
transforming growth factor β1
benazepril
candesartan
spontaneous hypertensive rats
