Apelin对血管紧张素Ⅱ诱导的心肌细胞肥大的作用及其机制  

Effect of Apelin on Angiotensin II-induced Cardiomyocyte Hypertrophy With its Mechanism in Experimental Rats

作　　者：周颖[1] 陈游洲[1] 乔树宾[1] 

机构地区：[1]北京协和医学院中国医学科学院国家心血管病中心阜外心血管病医院冠心病诊治中心,北京市100037

出　　处：《中国循环杂志》2014年第9期733-737,共5页Chinese Circulation Journal

摘　　要：目的：探讨Apelin对血管紧张素Ⅱ（AngⅡ）诱导的心肌细胞肥大的作用及其细胞内信号转导机制。方法：培养1-3 d新生Sprague-Dawley大鼠心肌细胞,给予AngⅡ刺激。在此基础上给予不同浓度Apelin。测定[3H]亮氨酸掺入量、细胞表面积以及总蛋白表达量评价心肌细胞肥大程度。免疫印迹法测定细胞B型尿钠肽、β肌球蛋白重链、活化T细胞的核因子3、钙调神经磷酸酶、磷酸化钙调神经磷酸酶、钙调蛋白激酶Ⅱ、磷酸化钙调蛋白激酶Ⅱ的蛋白表达水平。逆转录-聚合酶链反应法测定B型尿钠肽和β肌球蛋白重链mRNA表达水平。结果：Apelin可以抑制AngⅡ诱导的心肌细胞肥大,其作用呈剂量依赖性。同时,Apelin可以抑制AngⅡ诱导的B型尿钠肽和β肌球蛋白重链mRNA表达水平、B型尿钠肽和β肌球蛋白重链、活化T细胞的核因子3、磷酸化钙调神经磷酸酶、钙调蛋白激酶Ⅱ和磷酸化钙调蛋白激酶Ⅱ的蛋白表达水平升高,且均与Apelin浓度呈剂量依赖性。结论：Apelin可以抑制AngⅡ诱导的心肌细胞肥大,其机制与Ca2＋依赖的钙调神经磷酸酶信号转导通路有关。Objective： To explore the effect of apelin on angiotensin II （Ang II）-induced cardiomyocyte hypertrophy and intracellular signal transduction mechanism in experimental rats. Methods： The cardiomyocyte from 1 to 3 days neonatal rats were cultured with Ang II to induce the cardiomyocyte hypertrophy, and the cells were treated by apelin at different concentrations. The [3H] Leucine incorporation, cardiomyocyte surface area and total protein expression were analyzed to evaluate the degree of cardiomycyte hypertrophy. The protein expressions of intracellular BNP, β-MHC, nuclear factor 3 of activated T cells （NFATc3）, calcineurin, phosphocalcineurin, calmodulin kinase II （CaMK II） and phospho-CaMK II were assessed by Western blot analysis. The mRNA expressions of BNP andβ-MHC were examined by RT-PCR. Results： Apelin may inhibit Ang II induced cardiomyocyte hypertrophic response in a dose-dependent manner, the maximum inhibition was achieved at Ang II 1000 nmol/L. Meanwhile, apelin may inhibit Ang II-induced elevations of intracellular resting free calcium level, mRNA expressions of BNP andβ-MHC, protein expressions of NFATc3, phospho-calcineurin, CaMK II and phospho-CaMK II in a dose-dependent manner. Conclusion： Apelin may inhibit Ang II-induced cardiomyocyte hypertrophy in experimental rats which might be related to Ca2＋-dependent calcineurin signal pass ways.

关 键 词：血管紧张素Ⅱ 心肌细胞肥大 钙调神经磷酸酶 钙调蛋白依赖的蛋白激酶Ⅱ 

分 类 号：R363.16[医药卫生—病理学]