螺内酯抗钙调神经磷酸酶依赖的肾性高血压大鼠心肌肥厚作用机制  

The mechanism of spironolactone against calcineurin-dependent cardiac hypertrophy in renal hypertension rats

作　　者：常连庆[1] 谢晓华[1] 陈雯[1] 李朝晖 孙愚[1] 刘珍荣[1] 庞永正[2] 唐朝枢[2] 

机构地区：[1]解放军总医院南四科,北京100853 [2]北京大学第一医院心血管病研究所

出　　处：《中华心血管病杂志》2004年第3期254-257,共4页Chinese Journal of Cardiology

基　　金："十五"军队医药卫生科研基金重点课题资助项目( 0 2Z0 10 )

摘　　要：目的　观察螺内酯抗钙调神经磷酸酶 (calcineurin ,CaN)依赖的肾性高血压大鼠心肌肥厚的作用。方法　 2 0只Wistar大鼠随机分为 3组 :2组采用一肾一夹模型制造肾性高血压 ,其中螺内酯组 (n =7)予螺内酯灌胃 ,高血压组 (n =7)予水灌胃 ;假手术组 (n =6 )只予水灌胃。称重法测定心重比 ,发色底物法测CaN活性 ;半定量PCR测定各组心肌组织中心房利钠因子mRNA的水平 ,同时用免疫组织化学染色方法 ,观察心肌中CaN及活化T细胞核因子的表达。结果　肾性高血压大鼠经螺内酯灌胃 4周 ,其心重比较未干预组明显降低 (P <0 0 5 ) ,心房利钠因子mRNA水平较手术组明显降低 (P <0 0 5 ) ,与假手术组水平接近 ,心肌肥厚受到抑制 ,同时发现心肌中CaN活性较未干预组显著下降 ,免疫组化显示螺内酯干预组心肌中CaN及活化T细胞核因子表达降低。Objective To determine the mechanism of spironolactone against calcineurin dependent cardiac hypertrophy in renal hypertension rats. Methods The model of renal hypertension rats were established by the operation of “one kidney one clip”. Twenty Wistar rats was divided into 3 groups randomly. One operation group(spiro group, n =7) received oral administration of spironolactone for 4 weeks, while another operation group(op group , n =7) and the sham operation group(sham op group, n =6) received tap water. The ratio of left ventricular weight to body weight (LW/BW) and the activity of CaN in the cadiac tissue were measured. Half quantitative PCR was employed to determine the levels of atrial natriuretic factor(ANF) mRNA in cardiac tissue. The expression of calcineurin(CaN) and NFAT (nuclear factor of activated T cell ) in cardiac tissue was observed by immunohistochemical staining. Results The LW/BW and activity of CaN in spiro group decreased significantly compared with those in op group [LW/BW:(0 26±0 05)% vs (0 35±0 06)% , P <0 05;CaN:(0 14±0 04) A 410/mg protein vs (0 44±0 11) A 410/mg protein, P <0 05].ANF mRNA level in spiro group was similar to that in sham op group but much lower than that in op group ( P <0 05). The lower expression of CaN and NFAT in cardic tissure by immunohistochemical staining in spiro group was also observed. Conclusion The preventive mechanism of spirolactone upon cardiac hypertrophy is related to the decrease of CaN expression and its activity in cardiac tissue.

关 键 词：螺内酯 钙调神经磷酸酶 肾性高血压 大鼠 心肌肥厚 作用机制 

分 类 号：R541.3[医药卫生—心血管疾病]