钙调神经磷酸酶在肾血管性高血压大鼠心肌肥厚中的作用

Role of Calcineurin in the Progression of Cardiac Hypertrophy in Renovascular Hypertensive Rats

目的 探讨钙调神经磷酸酶 (CaN)在肾血管性高血压大鼠心肌肥厚中的作用及抑制CaN活性对心肌肥厚的影响。方法 制备两肾一夹肾血管性高血压大鼠模型 ,术后 2月 ,经心脏超声证实大鼠心肌肥厚后 ,分别予环孢菌素A(CsA)或培多普利治疗。观察CsA、培多普利对大鼠心肌肥厚程度 ,CaNmRNA、蛋白质表达和CaN活性的影响。结果 两肾一夹术后 2月 ,手术组大鼠左室后壁和室间隔厚度均较假手术组增高 2 1 % (P <0 0 1 ) ,CsA治疗后较治疗前分别下降 1 6 %和 1 4 % (P <0 0 1 ) ,培多普利治疗后左室后壁和室间隔厚度亦较治疗前下降。同时大鼠左室心肌CaNmRNA和蛋白质表达、CaN活性均显著下降。结论 CaN参与肾血管性高血压大鼠心肌肥厚 。

Objective The present study was to determine the role of calcineurin in the progression of cardiac hypertrophy in renovascular hypertensive rats and the effect of calcineurin inhibition on the regression of cardiac hypertrophy Methods The renovascular hypertension was induced by two kidney one clip methods Two months after the operation, cardiac hypertrophy was determined by echocardiography, then rats were treated with cyclosporine A(CsA) or perindopril for one month The changes of cardiac hypertrophy, calcineurin mRNA and protein expression and its activity were measured Results Two months after the operation, left ventricular posterior wall thickness and interventricular septum were significantly higher than those of the age matched sham operated rats The treatment of the rats with CsA or perindopril significantly attenuated these increases The mRNA and protein expression and the activity of calcineurin were decreased significantly by the treatments Conclusion Calcineurin plays a role in the progression of cardiac hypertrophy in renovascular hypertensive rats The inhibition of calcineurin could reverse the cardiac hypertrophy