钙调蛋白激酶Ⅱ信号转导途径在血管紧张素Ⅱ致心肌肥大反应中的调控作用  

Calmodulin Kinase Ⅱ Regulates the Cardiomyocyte Hypertrophic Responses Induced by Angiotensin Ⅱ

作　　者：王岚[1] 吕家高[2] 张存泰[2] 程冕[2] 刘念[2] 阮燕菲[2] 王琳[2] 

机构地区：[1]武汉市普爱医院心内科,武汉430033 [2]华中科技大学同济医学院附属同济医院心内科,武汉430030

出　　处：《华中科技大学学报（医学版）》2009年第1期27-30,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30470714)

摘　　要：目的研究钙调蛋白激酶Ⅱ(CAMKⅡ)途径在血管紧张素Ⅱ(AngⅡ)诱导乳鼠心肌细胞肥大反应中的作用。方法原代培养乳鼠心肌细胞,分为对照组(不加任何干预因素),肥厚组(AngⅡ刺激心肌细胞肥大),缬沙坦组(缬沙坦直接作用于心肌细胞)和预处理组(缬沙坦进行干预30 min后,加入AngⅡ刺激心肌细胞)。测定心肌细胞3H-亮氨酸掺入作为心肌细胞肥大的指标;用RT-PCR和Western blot法检测心肌细胞CAMKⅡδ的mRNA和蛋白质表达的水平。结果①AngⅡ在10-9～10-6mol/L范围内剂量依赖性地增加乳鼠心肌细胞的3H-亮氨酸掺入。选择10-7mol/L AngⅡ作用心肌细胞48 h为成功的心肌细胞肥厚模型。②AngⅡ(10-7mol/L)处理心肌细胞48 h,可使3H-亮氨酸掺入明显增加,该作用可被缬沙坦明显抑制。③与对照组相比,肥厚组心肌的CAMKⅡδmRNA水平显著增加;而缬沙坦预处理组较之肥厚组则显著下降。④与对照组相比,肥厚组心肌的CAMKⅡδ的蛋白质表达显著增加;而缬沙坦预处理组的CAMKⅡδ蛋白质表达水平较之肥厚组则显著下降。结论①CAMKⅡ信号转导通路激活是AngⅡ介导的心肌肥大反应重要环节之一。②缬沙坦抑制AngⅡ介导心肌肥大反应的机制可能部分是通过抑制CAMKⅡδ的表达而实现的。Objective To investigate the regulatory role of calmodulin kinase Ⅱ （CAMKⅡ） in cardiomyocyte hypertrophic response induced by angiotensin Ⅱ （Ang Ⅱ）. Methods Cultured cells derived from neonatal heart were divided into 4 groups： （1） normal control; （2） hypertrophic group： ceils were stimulated by AngⅡ（10^-7 mol/ L）; （3） valsartan group： cells were treated with valsartan （10^-6 mol/L）, and （4） pretreatment group., cells were treated with valsartan 30 min before adding Ang Ⅱ. Neonatal rat cardiomyocyte hypertrophic response was assayed by 3H-Leucine incorporation. The gene expression of CAMKδwas detected by RT-PCR and Western blot. Results Ang Ⅱ promoted 3 H-Leucine incorporation in a dose-dependent manner between 10^-9 --10^-6mol/ L. Cells treated with ang Ⅱ at 10^-7 mol/L for 48 h were chosen as hypertrophic cardiocyte model. Calmodulin kinase signaling might be the candidate target for therapy of hypertrophy and arrhythmias. The mRNA level of CAMK Ⅱδ was significantly increased in the hypertrophic group as compared with normal control and pretreatment groups. The protein level of CAMK Ⅱδ was significantly increased in the hypertrophic group as compared with normal control and pretreatment groups. Conclusion The activation of CAMK Ⅱ played an important role in cardiomyocytes hypertrophy induced by Ang Ⅱ. Valsartan prevented the hypertrophy of cardiomyocytes induced by Ang Ⅱ partially by inhibiting the expression of CAMK Ⅱδ.

关 键 词：钙调蛋白激酶Ⅱ 心肌细胞肥大 血管紧张素Ⅱ 缬沙坦 

分 类 号：R54[医药卫生—心血管疾病]