环孢菌素A对肾血管性高血压大鼠心肌肥厚和心功能的影响 一项关于CaN对心肌肥厚及心功能影响的随机对照实验

The effect of cyclosporine A on cardiac hypertrophy and function in renovascular hypertensive rats

目的通过建立两肾一夹高血压大鼠心肌肥厚模型,研究环孢菌素(CsA)对心肌肥厚及心功能的影响,以探讨钙调神经磷酸酶(CaN)在心肌肥厚进展中的作用。方法制备两肾一夹肾血管性高血压大鼠模型,术后2月,经心脏超声和部分大鼠(两肾一夹2月组)病理学证实心肌肥厚后,将大鼠随机分为两组,分别予生理盐水(两肾一夹3月组)或CsA(CsA组)腹腔注射,持续1月,并以假手术组作对照。观察大鼠左室重与胫骨长度比值、心肌细胞面积、左室后壁和室间隔厚度、CaN活性和心功能的改变。结果两肾一夹2月和3月组大鼠左室重与胫骨长度比值、心肌细胞面积、左室后壁和室间隔厚度较相应假手术组增高(F=12.4,13.0;P<0.05),CsA治疗组较两肾一夹2月和3月组均明显降低,与假手术组差异无显著性。CaN活性在两肾一夹2月和3月组均显著高于假手术组,CsA治疗后CaN活性下降(F=8.8;P<0.05)。各组射血分数、左室短轴缩短率及零负荷下等容收缩期心肌纤维收缩成分的缩短速度相似(F=1.0,1.1;P>0.05),CsA组左室舒张末压、等容舒张期压力下降时间常数较两肾一夹3月组显著下降(F=3.4,10,3;P<0.05)。结论CaN参与了肾血管性高血压心肌肥厚进展,CsA可逆转心肌肥厚,改善心脏舒张功能。

Aim Calcineurin plays a critical role in the development of cardiac hypertrophy.However,it is not known if calcineurin is required for the long term maintenance of cardiac hypertrophy,or hypertrophy could be reversed by the inhibition of calcineurin in renovascular hypertensive rats. This study was to determine the effect of calcineurin inhibitor cyclosporine A (CsA) on the regression of cardiac hypertrophy and amelioration of cardiac function in rats.Methods The renovascular hypertension was induced by two kidney one clip methods.Two months after the operation,cardiac hypertrophy was determined by echocardiography and histological analysis performed in some rats(2K1C 2M),then the rats were subdivided into 2 groups:(1)3 month two kidney one clip group(2K1C 3M):rats received 9 g/L NaCl per day for one month; (2) CsA treated group(CsA):rats were treated with CsA (20 mg/(kg· d) for one month, sham operated rats were used as control.The ratio of left ventricular weight to tibial length, cardiomyocyte cross sectional area, thickness of left posterior wall and interventricular septum, calcineurin activity and cardiac function were measured.Results The ratio of left ventricular weight to tibial length, the cardiomyocyte cross sectional area, the thickness of left ventricular posterior wall and interventricular septum of 2K1C 2M and 2K1C 3M were significantly higher than those of the corresponding sham operated groups. Treatment of the rats with CsA attenuated the increases, compared with either those of 2K1C 3M or 2K1C 2M. Calcineurin activity was increased in 2K1C 2M and 2K1C 3M, and it decreased in CsA treated group. The ejection fraction and fractional shortening, Vmax did not differ significantly among all the groups. Time constant and left ventricular end diastolic pressure decreased significantly in the rats treated with CsA compared to those of the 2K1C 3M rats.Conclusion Inhibition of calcineurin can reverse cardiac hypertrophy and improve cardiac diastolic function in renovascular hypertensive rats.