缬沙坦对肾血管性高血压大鼠心肌钙蛋白酶I、钙调神经磷酸酶和钙／钙调素依赖蛋白激酶Ⅱδ的影响  

Role of valsartan on myocardial Calpain I , calcineurin and Ca/calmodulin-dependent protein kinase Ⅱδ expression of renovascular hypertensive rats

作　　者：陆尽亚[1] 朱健华[1] 秦小同[1] 于小红[1] 盛红专[1] 

机构地区：[1]南通大学附属医院心内科,226001

出　　处：《中华心血管病杂志》2012年第6期511-515,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30971224,30971223）;南通市科技局资助项目（S2009025）

摘　　要：目的通过检测肾血管性高血压大鼠心肌肥厚过程中钙蛋白酶I（CalpainI）、钙调神经磷酸酶（calcineurin，CaN）、钙／钙调素依赖蛋白激酶Ⅱ（Ca／calmodulin—dependentproteinkinaseⅡ，CaMKⅡ）8亚型A、B、C3种变异体可变剪接的改变，并观察血管紧张素受体阻断剂缬沙坦对心肌肥厚和CalpainI、CaN及CaMKⅡδ的影响，探讨缬沙坦预防心肌肥厚的可能机理。方法SD大鼠，构建两肾一夹模型，随机分为假手术组、两肾一夹组和缬沙坦组（在两。肾一夹基础上每日予缬沙坦干预），观察大鼠心肌肥厚程度改变，RT—PCR法检测CaNmRNA表达和CaMKⅡδ可变剪接变化，免疫印迹法检测CaN、CalpainI蛋白质表达改变，并测定CaN活性变化。结果两肾一夹组大鼠左心室质量／体质量显著高于假手术组（提示大鼠发生心肌肥厚），同时大鼠心肌CalpainI蛋白质表达、CaNmRNA和蛋白质表达及CaN活性显著高于假手术组（P均〈0．05），CaMKll8的可变剪接表现为CaMKⅡδA、BmRNA表达均高于假手术组（P均〈0．01），CaMKⅡδCmRNA表达则低于假手术组（P〈0．01）。缬沙坦组大鼠左心室质量／体质量显著低于两。肾一夹组（提示心肌肥厚改善），同时大鼠心肌CalpainI蛋白质表达、CaNmRNA和蛋白质表达及CaN活性均显著低于两肾一夹组（P均〈0．05），CaMKⅡ8的可变剪接表现为CaMKⅡδA、BmRNA表达均低于两肾一夹组（P均〈0．01），CaMKⅡδcmRNA表达则高于两肾一夹组（P〈0．01）。结论CalpainI、CaN信号传导通路和CaMKⅡδ的可变剪接参与介导了肾血管性高血压大鼠心肌肥厚的发生。缬沙坦可通过调控这些胞内信号传导通路预防肾血管性高血压大鼠心肌肥厚。Objective To determine the protein expression of Calpain I , mRNA and protein expressions and activity of calcineurin, and the alternative splicing of Ca/ealmodulin-dependent protein kinase Ⅱ（CaMK Ⅱ ） . in the hypertrophic heart, and to investigate the effect of angiotensin Ⅱ type 1 receptor blocker valsartan （Val） on cardiac hypertrophy and the level of Calpain I , calcineurin and CaMK Ⅱδ in renovascular hypertensive rats model. Methods Rats were randomly divided into shamoperated control （ n = 8 ）, hypertension （ n= 8 ） and hypertension plus Val （ n = 8, 30 mg · kg^- 1 · d^ - 1 ）. The renovaseular hypertension was induced by two kidney-one clip methods in rats. The ratio of left ventricular weight to body weight was measured, the mRNA expression of ealeineurin and alternative splicing of CaMK Ⅱδ were determined by RT-PCR, the protein expression of Calpain I and calcineurin were measured by Western blot and the activity of caleineurin activity was assayed by a specialized kit. Results Eight weeks after procedure, hypertension rats developed significantly cardiac hypertrophy, and the protein expression of Calpain I , mRNA and protein expression and the activity of calcineurin were significantly increased compared sham-operated control rats （ all P 〈 0. 01 ）, the mRNA expression of CaMK ⅡδA and B increased, CaMK Ⅱδ mRNA decreased （P 〈 0. 01 ）. Treatment with valsartan effectively attenuated cardiac hypertrophy and reversed hypertension induced changes on myocardial Calpain I, calcineurin and CaMKⅡδ. Conclusion Valsartan attenuates cardiac hypertrophy in renovascular hypertensive rats, possibly through inhibiting Calpain I , calcineurin and CaMK Ⅱδ signaling pathways.

关 键 词：高血压 肾血管性 卡配因 钙神经素 钙-钙调素依赖蛋白激酶 缬沙坦 

分 类 号：R965[医药卫生—药理学]