伊贝沙坦和培垛普利对大鼠压力负荷性心肌肥厚的影响

Effects of irbesartan and perindopril on pressure overload-induced cardiac hypertrophy in rats

目的 :探讨钙调神经磷酸酶和钙泵活性在大鼠压力负荷性心肌肥厚时的变化及伊贝沙坦和培垛普利对它们的影响。方法 :4 0只雄性SD大鼠随机分为 5组。除假手术组外 ,其余 4组大鼠采用腹主动脉部分结扎法造成压力负荷性心肌肥厚模型 ,术后 1周分别用下列药物开始灌胃 :假手术组和对照组生理盐水 2mL·kg-1·d-1,伊贝沙坦组 2 0mg·kg-1·d-1,培垛普利组 2mg·kg-1·d-1及联合用药组 (培垛普利 2mg·kg-1·d-1,伊贝沙坦 2 0mg·kg-1·d-1)。用药 6周后检测左室质量指数、心肌细胞横径、心肌钙调神经磷酸酶及钙泵活性 ,免疫组化测定心肌钙调神经磷酸酶的表达。结果 :联合用药组LVMI显著低于对照组及单用伊贝沙坦或培垛普利药组 ,各用药组TDM及钙调神经磷酸酶活性显著低于对照组 ,对照组心肌肌浆网钙泵活性显著低于其他各组 ,联合用药组钙泵活性明显高于单独用药组。免疫组化显示对照组心肌组织钙调神经磷酸酶表达显著高于其他各组。相关分析显示LVMI与TDM、CaN均呈显著正相关 ,与钙泵活性呈负相关。结论 :伊贝沙坦和培垛普利可抑制钙调神经磷酸酶活性 ,增加心肌肌浆网钙泵活性 ,联合应用对减轻心肌肥厚有协同作用。

AIM: To observe the effects of irbesartan and perindopril on pressure-overload cardiac hypertrophy in rats. METHODS: 40 male adult Sprague Dawley rats were divided into 5 groups. One was sham operation group, other four were aortic banding groups. One week after operation, all rats were gavaged with normal saline, perindopril, irbesartan or combination of perindopril and irbesartan. Morphometric determination, calcineurin (CaN) expression, CaN and sarcoplasmic reticulum (SR) Ca 2+-ATPase activity were performed at the end of 6 weeks of drug intervention. RESULTS: Left ventricular mass index (LVMI), transverse diameter of myocardical cell (TDM), CaN activity were remarkably decreased after drug intervention and this decrease was most remarkable in the combination group. SR Ca 2+-ATPase activity increased after drug intervention, especially in the combination group. CaN expression in myocardium were remarkably decreased after drug intervention. LVMI was positively correlated with TDM and CaN, negatively correlated with SR Ca 2+-ATPase. CONCLUSION: Both irbesartan and perindopril decrease CaN activity, increase SR Ca 2+-ATPase activity and combination of them has synergic effects on regressing of ventricular hypertrophy.