赖诺普利与氯沙坦预防压力负荷性心肌肥厚的实验研究  

Prevention of myocardial hypertrophy in pressure overload rats by Lisinopril and Losartan

作　　者：李东野[1] 周俊[1] 丁茜[1] 陈清枝[1] 钱文浩[1] 夏勇[1] 潘德锋[1] 史春志[1] 

机构地区：[1]徐州医学院附属医院心内科,221002

出　　处：《江苏医药》2003年第10期731-734,共4页Jiangsu Medical Journal

摘　　要：目的　探讨大鼠心肌肥厚时心血管重构的结构、生化改变及赖诺普利与氯沙坦对心血管重构的预防作用。方法　膈下腹主动脉缩窄法建立大鼠心肌肥厚模型。假手术组、模型组、降压和非降压剂量赖诺普利与氯沙坦在术后第 2天用药至 30天后 ,检测平均动脉压 (MAP)、心肌肥厚程度及局部心肌组织一氧化氮 (NO)、一氧化氮合酶 (NOS)和胶原蛋白含量。结果　 (1)与假手术组相比 ,模型组MAP、左室重量 (LVW )、左室重量指数 (LVMI)、心肌细胞横径 (TDM )、胶原蛋白分别提高 2 8 6 %、2 0 5 %、2 6 9%、17 9%、5 4 4 % (P <0 0 1) ;NO、NOS分别降低 5 3 4 %、5 1 2 % (P <0 0 1)。 (2 )降压剂量赖诺普利与氯沙坦和非降压剂量氯沙坦干预后 ,LVW、LVMI、TDM、NO、NOS、胶原蛋白含量与假手术组无明显差异。非降压剂量赖诺普利可使LVW、LVMI和TDM下降 ,但仍高于假手术组 (P <0 0 1) ,NO、NOS改善不明显 ;(3)LVMI与MAP、胶原蛋白含量均呈正相关 (分别为r =0 784 1,r =0 8177,P <0 0 1) ,与NO显著负相关 (r =- 0 7730 ,P <0 0 1)。结论　心血管重构与血压、心脏间质成分及NO有密切关系 ;赖诺普利预防心肌肥厚可能是血流动力学和非血流动力学因素共同作用的结果 ;Objective To investigate the structural and biochemical change of cardiovascular remodeling and examine the preventive effects of Losartan and Lisinopril in pressure overload rats.Methods Pressure overload model was produced by abdominal aortic coarctation in rats.Measurements were done for the mean arterial pressure(MAP),the change of myocardial hypertrophy,nitric oxide(NO),nitric oxide synthase(NOS)and collagen protein of local myocardium in six groups including Group Sham,Group Model,hypotensive and sub-hypotensive dose groups Lisinopril and Losartan.Lisinopril and Losartan had been given by daily gavage for thirty days since the first day after operation.Results Compare with Group Sham,MAP,left ventricular weights(LVW),left ventricular mass index(LVMI),transverse diameter myocytes(TDM)and collagen protein in Group Model increased respectively 28.6%,20.5%,26.9%,17.9% and 54.4%(P<0.01) while NO and NOS decreased by 53.4% and 51.2%(P<0.01).Hypotensive dose Lisinopril,Losartan and sub-hypotensive dose Losartan could prevent cardiovascular remodeling and increase NO and NOS completely.Sub-hypotensive dose Lisinopril was able to lighten myocardial hypertrophy,but it significantly differed from Group Sham(P<0.01),while NO and NOS didn't improve.LVMI was positively related to MAP and collagen protein respectively(r=0.7841,r=0.8177,P<0.01)while it was negatively related to NO(r=0.7730,P<0.01).Conclusions Cardiovascular remodeling had intimate connection with MAP,NO and collagen protein;The effect of Lisinopril on myocardial hypertrophy might be common action of hemodynamic stress and non-hemodynamic stress factors while the effect of Losartan could rely on non-hemodynamic stress factors.

关 键 词：赖诺普利 心肌肥厚 氯沙坦 心血管重构 手术 一氧化氮合酶(NOS) 降压 负相关 心肌细胞 胶原蛋白 

分 类 号：R544[医药卫生—心血管疾病] R542.2[医药卫生—内科学]