Kang Lan, Ge Chang-Jiang, Hu Shen-Jiang
Institute of Cardiology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
Pharmacology. 2007;80(2-3):120-6. doi: 10.1159/000103251. Epub 2007 May 29.
This study was designed to investigate whether atorvastatin has a beneficial effect on left ventricular (LV) remodeling in spontaneously hypertensive rats (SHR), and then explore the underlying mechanisms involved. 12 SHRs were randomized to receive either distilled water (SHR group, n = 6) or atorvastatin (ATV group, n = 6) for 10 weeks. Age-matched Wistar-Kyoto rats (WKY) gavaged by distilled water were used as normal controls (WKY group, n = 6). By using these rats, we observed the effects of atorvastatin on LV hypertrophy and fibrosis, and investigated atorvastatin-induced cell apoptosis and p27 protein expression. In addition, the serum lipid concentration and blood pressure level were also measured in this study. 10 weeks later, a significant decrease in the cardiosomatic ratio, LV weight to body weight ratio and cardiomyocyte transverse diameter, as well as myocardial hydroxyproline and collagen content was observed in the atorvastatin-treated SHR. In addition, atorvastatin increased the positive rate of cell apoptosis and p27 protein expression. A decreased serum lipid concentration and a reduced systolic blood pressure level were also found in the atorvastatin-treated SHR. These findings demonstrated a beneficial effect of atorvastatin on adverse LV remodeling in SHR, and the induction of cell apoptosis and upregulation of p27 protein may serve as the underlying mechanisms of this action.
本研究旨在探讨阿托伐他汀对自发性高血压大鼠(SHR)左心室(LV)重构是否具有有益作用,并进而探究其潜在机制。将12只SHR随机分为两组,分别给予蒸馏水(SHR组,n = 6)或阿托伐他汀(ATV组,n = 6),持续10周。以经蒸馏水灌胃的年龄匹配的Wistar-Kyoto大鼠(WKY)作为正常对照(WKY组,n = 6)。利用这些大鼠,我们观察了阿托伐他汀对左心室肥厚和纤维化的影响,并研究了阿托伐他汀诱导的细胞凋亡及p27蛋白表达情况。此外,本研究还测量了血清脂质浓度和血压水平。10周后,在接受阿托伐他汀治疗的SHR中观察到心脏体重比、左心室重量与体重比及心肌细胞横径显著降低,同时心肌羟脯氨酸和胶原蛋白含量也显著降低。此外,阿托伐他汀增加了细胞凋亡阳性率及p27蛋白表达。在接受阿托伐他汀治疗的SHR中还发现血清脂质浓度降低及收缩压水平下降。这些研究结果表明阿托伐他汀对SHR的不良左心室重构具有有益作用,诱导细胞凋亡及上调p27蛋白可能是其作用的潜在机制。