CAJ | 학술논문

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 (Calpain Ⅰ)、钙调神经磷酸酶( calcineurin,CaN)、钙/钙调素依赖蛋白激酶Ⅱ(Ca/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)δ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CaN mRNA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Calpain Ⅰ蛋白质表达、CaN mRNA和蛋白质表达及CaN活性显著高于假手术组(P均＜0.05),CaMKⅡδ的可变剪接表现为CaMKⅡδA、B mRNA表达均高于假手术组(P均＜0.01),CaMKⅡδC mRNA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Calpain Ⅰ蛋白质表达、CaN mRNA和蛋白质表达及CaN活性均显著低于两肾一夹组(P均＜0.05),CaMKⅡδ的可变剪接表现为CaMKⅡδA、B mRNA表达均低于两肾一夹组(P均＜0.01),CaMKⅡδC mRNA表达则高于两肾一夹组(P＜0.01).结论 Calpain Ⅰ、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.
목적 통과검측신혈관성고혈압대서심기비후과정중개단백매Ⅰ (Calpain Ⅰ)、개조신경린산매( calcineurin,CaN)、개/개조소의뢰단백격매Ⅱ(Ca/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)δ아형A、B、C3충변이체가변전접적개변,병관찰혈관긴장소수체조단제힐사탄대심기비후화CalpainⅠ、CaN급CaMKⅡδ적영향,탐토힐사탄예방심기비후적가능궤리.방법 SD대서,구건량신일협모형,수궤분위가수술조、량신일협조화힐사탄조(재량신일협기출상매일여힐사탄간예),관찰대서심기비후정도개변,RT-PCR법검측CaN mRNA표체화CaMKⅡδ가변전접변화,면역인적법검측CaN、CalpainⅠ단백질표체개변,병측정CaN활성변화.결과 량신일협조대서좌심실질량/체질량현저고우가수술조(제시대서발생심기비후),동시대서심기Calpain Ⅰ단백질표체、CaN mRNA화단백질표체급CaN활성현저고우가수술조(P균＜0.05),CaMKⅡδ적가변전접표현위CaMKⅡδA、B mRNA표체균고우가수술조(P균＜0.01),CaMKⅡδC mRNA표체칙저우가수술조(P＜0.01).힐사탄조대서좌심실질량/체질량현저저우량신일협조(제시심기비후개선),동시대서심기Calpain Ⅰ단백질표체、CaN mRNA화단백질표체급CaN활성균현저저우량신일협조(P균＜0.05),CaMKⅡδ적가변전접표현위CaMKⅡδA、B mRNA표체균저우량신일협조(P균＜0.01),CaMKⅡδC mRNA표체칙고우량신일협조(P＜0.01).결론 Calpain Ⅰ、CaN신호전도통로화CaMKⅡδ적가변전접삼여개도료신혈관성고혈압대서심기비후적발생.힐사탄가통과조공저사포내신호전도통로예방신혈관성고혈압대서심기비후.
Objective To determine the protein expression of Calpain Ⅰ,mRNA and protein expressions and activity of calcineurin,and the alternative splicing of Ca/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ ) δ in the hypertrophic heart,and to investigate the effect of angiotensin Ⅱ type 1receptor blocker valsartan (Val) on cardiac hypertrophy and the level of Calpain Ⅰ,calcineurin and CaMK Ⅱ δ in renovascular hypertensive rats model.Methods Rats were randomly divided into sharmoperated control (n =8),hypertension (n =8) and hypertension plus Val (n =8,30 mg· kg-1 · d-1 ).The renovascular 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 calcineurin and alternative splicing of CaMK Ⅱ δ were determined by RT-PCR,the protein expression of Calpain Ⅰ and calcineurin were measured by Western blot and the activity of calcineurin 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 Ⅱ δA and B increased,CaMK ⅡδC mRNA decreased ( P ＜0.01 ).Treatment with valsartan effectively attentated 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.