Sheng Li, Ye Ping, Liu Yong-xue
Department of Geriatric Cardiology and Nephrology, Chinese PLA General Hospital, Beijing 100853, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2005 Dec;33(12):1080-4.
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 alpha, gamma) subtypes in vitro.
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, interleukin1beta (IL-1beta) and PPARalpha, gamma was measured by reverse transcription-polymerase chain reaction (RT-PCR).
Changes of MC were detected induced by Ang II, including increases in surface area, mRNA expression of ANP, BNP, MMP9, MMP2 and IL-1beta, and (3)H-leucine incorporation, as well as a decrease in mRNA expression of PPARalpha, gamma. Treatment with atorvastatin inhibited the changes above in a dose-dependent manner, but no change was found in treated with DMSO.
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 alpha and gamma maybe involved in this process.
研究阿托伐他汀对血管紧张素 II（Ang II）诱导的心肌细胞（MC）肥大的影响以及体外过氧化物酶体增殖物激活受体α、γ（PPARα、γ）亚型mRNA表达的变化。
用Ang II诱导新生大鼠MC肥大并给予阿托伐他汀处理。借助NIH Image J软件分析MC表面积，通过³H-亮氨酸掺入法检测MC中蛋白质合成速率。采用逆转录-聚合酶链反应（RT-PCR）检测心房利钠肽（ANP）、脑利钠肽（BNP）、基质金属蛋白酶（MMP）9、MMP2、白细胞介素1β（IL-1β）以及PPARα、γ的mRNA表达。
检测到Ang II诱导MC发生变化，包括表面积增加、ANP、BNP、MMP9、MMP2和IL-1β的mRNA表达增加以及³H-亮氨酸掺入增加，同时PPARα、γ的mRNA表达降低。阿托伐他汀处理以剂量依赖方式抑制上述变化，但二甲基亚砜处理未发现变化。
阿托伐他汀在体外可抑制心肌肥大。提示阿托伐他汀在预防和治疗如心肌肥大等心脏疾病方面具有潜在作用，且PPARα和γ可能参与此过程。
