阿托伐他汀抑制心肌细胞肥大并增强过氧化体增殖物激活型受体β/δ的表达
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国家自然科学基金(30270551)


Atorvastatin Inhibits Hypertrophy and Upragulate the Expression of Peroxisome Proliferator-Activated Receptors beta/delta in Neonatal Rat Cardiomyocytes in Vitro
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    摘要:

    目的探讨阿托伐他汀在体外对血管紧张素Ⅱ介导的肥大心肌细胞的作用,分析过氧化物酶体增殖物激活型受体β/δ在其中的可能作用。方法采用体外原代培养新生大鼠的心室肌细胞方法,用血管紧张素Ⅱ诱导建立心肌肥厚模型,在模型中加入不同浓度的阿托伐他汀,通过数码相机摄影扫描,以测量软件NIH Image J测定分析心肌细胞表面积,利用氚标亮氨酸掺入方法检测心肌细胞蛋白合成速率及使用逆转录聚合酶链反应半定量测定心房钠尿肽、脑钠尿肽和过氧化体增殖物激活型受体β/δmRNA的表达变化。结果血管紧张素Ⅱ可使体外培养的心肌细胞表面积(p<0.01)和氚标亮氨酸的掺入增加(p<0.01),升高心房钠尿肽和脑钠尿肽(均为p<0.01)的表达,过氧化体增殖物激活型受体β/δ(p<0.01)表达下降;阿托伐他汀可逆转上述变化并呈剂量依赖性(p<0.05),而作为溶剂的二甲亚砜对心肌肥厚无影响(p>0.05)。结论阿托伐他汀具有抑制血管紧张素Ⅱ介导的体外心肌细胞肥大的作用,过氧化体增殖物激活型受体β/δ很可能参与该过程。

    Abstract:

    Aim To investigate the effects of atorvastatin on AngⅡ-induced hypertrophy myocytes and the changes of mRNA expression of peroxisome proliferators-activated receptorβ/δ in vitro. Methods Hypertrophy in neonatal rat cardiac myocytes(MC) was established with angiotensin Ⅱ(Ang Ⅱ) and treated with atorvastatin.The surface area of MC was analyzed by the aid of NIH Image J software,and the synthetic rate of protein in MC was detected by 3H-leucine incorporation.mRNA expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP) and peroxisome proliferatoractivated receptor beta/delta subtypes(PPARβ/δ) was measured by reverse transcription-polymerase chain reaction(RT-PCR). Results In the condition of hypertrophy,increases of surface area(p<0.01),mRNA expression of ANP,BNP(both p<0.01),and ~3H-leucine incorporation(p<0.01);and a decrease of mRNA expression of PPARβ/δ(p<0.01) in MC were detected,but no changes in treated with DMSO(p>0.05).Atorvatatin inhibited the changes above,reduced mRNA expression of ANP and BNP,elevated mRNA expression of PPARβ/δ in a dose-dependent manner(p<0.05). Conclusions It was suggested that atorvastatin has a potential role in the prevention and treatment of cardiac hypertrophy,and PPAR β/δ may be involved in it.

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盛莉,叶平,刘永学,赵云山,崔春平,尚明美,吴芳明.阿托伐他汀抑制心肌细胞肥大并增强过氧化体增殖物激活型受体β/δ的表达[J].中国动脉硬化杂志,2005,13(6):681~684.

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  • 收稿日期:2005-07-20
  • 最后修改日期:2005-11-15
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