阿托伐他汀上调过氧化物酶体增殖物活化型受体α、γ表达及抑制心肌细胞肥大的作用  

Atorvastatin upregulates the expression of PPAR alpha/gamma and inhibits the hypertrophy of cardiac myocytes in vitro

作　　者：盛莉[1] 叶平[1] 刘永学[2] 

机构地区：[1]中国人民解放军总医院老年心肾科,北京100853 [2]军事医学科学院放射医学研究所

出　　处：《中华心血管病杂志》2005年第12期1080-1084,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助(30270551)

摘　　要：目的探讨阿托伐他汀在体外对血管紧张素Ⅱ(AngⅡ)介导的肥大心肌细胞的作用,分析过氧化物酶体增殖物活化型受体(PPAR)α、γ在其中的可能作用。方法体外培养新生大鼠的心室肌细胞,用AngⅡ诱导建立心肌肥厚模型,在模型中加入不同浓度阿托伐他汀,用软件分析观察心肌细胞表面积,应用3H-亮氨酸掺入实验检测心肌细胞蛋白合成速率及使用RT-PCR半定量测定心钠素、脑钠素、基质金属蛋白酶9、基质金属蛋白酶2、白介素1β和PPARα、γmRNA的表达变化。结果AngⅡ可使体外培养的心肌细胞表面积和3H-亮氨酸的掺入增加,升高心钠素、脑钠素、基质金属蛋白酶9、基质金属蛋白酶2和白介素1β的表达,PPARα、γ表达下降;阿托伐他汀可逆转上述变化并呈剂量依赖性,而作为溶剂的DMSO对心肌肥厚无影响。结论阿托伐他汀具有抑制AngⅡ介导的体外心肌细胞肥大的作用,PPARα及PPARγ很可能参与该过程。Objective To investigate the effects of atorvastatin on angiotensin Ⅱ （Ang Ⅱ ）- induced hypertrophy of cardiac myocytes （MC） and the changes of mRNA expression of peroxisome proliferators-activated receptor alpha, gamma （PPAR α, γ） subtypes in vitro. Methods Hypertrophy in neonatal rat MC was established with 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 3^H-leucine incorporation, mRNA expression of atrial natriuretic peptide （ANP）, brain natriuretic peptide （BNP）, matrix metalloproteinase （MMP） 9, MMP2, interleukin1β （IL-1β） and PPARα,γ was measured by reverse transcription-polymerase chain reaction （ RT-PCR ） . Results Changes of MC were detected induced by Ang Ⅱ , including increases in surface area, mRNA expression of ANP, BNP, MMPg, MMP2 and IL-1β, and 3^ H-leucine incorporation, as well as a decrease in mRNA expression of PPARα, γ Treatment with atorvastatin inhibited the changes above in a dose-dependent manner, but no change was found in treated with DMSO. Conclusion Atorvastatin inhibits cardiac hypertrophy in vitro. It is suggested that atorvastatin has a potential role in the prevention and treatment of cardiac diseases such as cardiac hypertrophy, and PPAR ot and γ maybe involved in this process.

关 键 词：降血脂药 心肌 肥大 过氧化物酶体类 过氧化物酶体增殖物 心肌细胞肥大 阿托伐他汀 受体Α 活化 基质金属蛋白酶9 

分 类 号：R542.2[医药卫生—心血管疾病]