CAJ | 학술논문

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。
목적：탐토Apelin대혈관긴장소Ⅱ（AngⅡ）유도적심기세포비대적작용급기세포내신호전도궤제。 　　방법：배양1~3 d신생Sprague-Dawley대서심기세포，급여AngⅡ자격。재차기출상급여불동농도Apelin。측정[3H]량안산참입량、세포표면적이급총단백표체량평개심기세포비대정도。면역인적법측정세포B형뇨납태、β기구단백중련、활화T세포적핵인자3、개조신경린산매、린산화개조신경린산매、개조단백격매Ⅱ、린산화개조단백격매Ⅱ적단백표체수평。역전록-취합매련반응법측정B형뇨납태화β기구단백중련mRNA표체수평。 　　결과：Apelin가이억제AngⅡ유도적심기세포비대，기작용정제량의뢰성。동시，Apelin가이억제AngⅡ유도적B형뇨납태화β기구단백중련mRNA표체수평、B형뇨납태화β기구단백중련、활화T세포적핵인자3、린산화개조신경린산매、개조단백격매Ⅱ화린산화개조단백격매Ⅱ적단백표체수평승고，차균여Apelin농도정제량의뢰성。 　　결론：Apelin가이억제AngⅡ유도적심기세포비대，기궤제여Ca2+의뢰적개조신경린산매신호전도통로유관。
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, phospho-calcineurin, 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.