Zheng Xia, Hu Shen-jiang
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Acta Pharmacol Sin. 2005 Jun;26(6):696-704. doi: 10.1111/j.1745-7254.2005.00105.x.
To investigate the effect of simvastatin on the cardiac contractile function and the alteration of gene and protein expression of the sarcoplasmic calcium regulatory proteins, including sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and ryanodine receptor 2 (RyR2) in rat hearts.
Langendorff-perfused rat hearts were subjected to 60-min perfusion with different concentrations of simvastatin (1, 3, 10, 30, or 100 microml/L), and the parameters of cardiac function such as left ventricular developed pressure (LVDP), +dp/dtmax, and -dp/dtmax were determined. The cultured neonatal rat ventricular cardiomyocytes were incubated with simvastatin (1, 3, 10, 30, and 100 micromol/L) for 1 h or 24 h. The levels of SERCA, PLB, and RyR2 expression were measured by reverse transcription-polymerase chain reaction and Western blot. Cytotoxic effect of simvastatin on ventricular cardiomyocytes was assessed by the MTT colorimetric assay.
LVDP, +dp/dtmax, and -dp/dtmax of hearts were increased significantly after treatment with simvastatin 3, 10, and 30 micromol/L. In simvastatin-treated isolated hearts, the levels of mRNA expression of SERCA and RyR2 were elevated compared with the control (P<0.05), while the mRNA expression of PLB did not change. After the cultured neonatal rat ventricular cardiomyocytes were incubated with 3, 10, 30, and 100 mumol/L simvastatin for 1 h, SERCA and RyR2 mRNA expressions of cardiomyocytes rose, but there was no alteration in protein expressions. However, with the elongation of simvastatin treatment to 24 h, the protein expression of SERCA and RyR2 were also elevated. Additionally, simvastatin (1-30 micromol/L) had no influence on cell viability of cultured cardiac myocytes, but simvastatin 100 micromol/L inhibited the cell viability.
Simvastatin improved cardiac performance accompanied by the elevation of SERCA and RyR2 gene and protein expression.
研究辛伐他汀对大鼠心脏收缩功能以及肌浆网钙调节蛋白（包括肌浆网Ca2 + -ATP酶（SERCA）、受磷蛋白（PLB）和兰尼碱受体2（RyR2））基因和蛋白表达变化的影响。
采用Langendorff灌注的大鼠心脏，用不同浓度（1、3、10、30或100 μmol/L）的辛伐他汀进行60分钟灌注，测定心功能参数，如左心室舒张末压（LVDP）、+dp/dtmax和-dp/dtmax。将培养的新生大鼠心室肌细胞与辛伐他汀（1、3、10、30和100 μmol/L）孵育1小时或24小时。通过逆转录-聚合酶链反应和蛋白质印迹法测定SERCA、PLB和RyR2的表达水平。采用MTT比色法评估辛伐他汀对心室肌细胞的细胞毒性作用。
用3、10和30 μmol/L辛伐他汀处理后，心脏的LVDP、+dp/dtmax和-dp/dtmax显著升高。在辛伐他汀处理的离体心脏中，SERCA和RyR2的mRNA表达水平较对照组升高（P<0.05），而PLB的mRNA表达未改变。培养的新生大鼠心室肌细胞与3、10、30和100 μmol/L辛伐他汀孵育1小时后，心肌细胞的SERCA和RyR2 mRNA表达升高，但蛋白表达无变化。然而，随着辛伐他汀处理时间延长至24小时，SERCA和RyR2的蛋白表达也升高。此外，辛伐他汀（1 - 30 μmol/L）对培养心肌细胞的细胞活力无影响，但100 μmol/L辛伐他汀抑制细胞活力。
辛伐他汀改善心脏功能，同时伴有SERCA和RyR2基因及蛋白表达的升高。
