Zhao Xiao-Yan, Li Ling, Zhang Jin-Ying, Liu Gang-Qiong, Chen Ya-Li, Yang Pei-Ling, Liu Rui-Yun
Department of Cardiology, the First Affiliated Hospital, Zhengzhou University, China.
Int Heart J. 2010;51(6):426-31. doi: 10.1536/ihj.51.426.
Statins improve left ventricular (LV) remodeling in spontaneously hypertensive rats (SHRs). This study was designed to investigate the effects of atorvastatin administered in the early stage on LV remodeling in SHRs, and to explore the underlying mechanisms.Sixteen male 8-week-old SHRs were randomized to receive distilled water (SHR-DW) or atorvastatin (SHR-ATV) for 12 weeks. Age-matched male Wistar-Kyoto (WKY) rats gavaged with distilled water served as controls. LV remodeling was evaluated, myocardial CTGF expression levels were detected using Western blotting, and cardiomyocyte apoptosis was detected with the TUNEL method.Compared with WKY and SHR-DW, atorvastatin treatment significantly decreased systolic blood pressure in SHRs; atorvastatin significantly inhibited LV remodeling, as indicated by the reduced LV weight/body weight ratio (SHR-ATV: 4.0 ± 0.4 versus SHR-DW: 4.7 ± 0.4 mg/g, P < 0.05), cardiomyocyte diameter (SHR-ATV: 16.2 ± 2.8 versus SHR-DW: 19.0 ± 1.0 µm, P < 0.05), and interstitial fibrosis (SHR-ATV: 3.3 ± 2.1 versus SHR-DW: 4.5 ± 1.8%, P < 0.05). Compared with WKY, myocardial CTGF expression was significantly increased and cardiomyocyte apoptosis decreased in SHRs. Compared with the SHR-DW group, atorvastatin treatment significantly inhibited myocardial CTGF expression (SHR-ATV: 0.69 ± 0.21 versus SHR-DW: 1.12 ± 0.27, P < 0.05) and induced cardiomyocyte apoptosis in SHRs (SHR-ATV: 5.2 ± 0.6 versus SHR-DW: 1.9 ± 0.3%, P < 0.05).The results indicate that early-stage administration of atorvastatin effectively prevented LV remodeling in SHRs, and that inhibition of myocardial CTGF expression and induction of cardiomyocyte apoptosis may be the underlying mechanisms.
他汀类药物可改善自发性高血压大鼠（SHR）的左心室（LV）重构。本研究旨在探讨早期给予阿托伐他汀对SHR左心室重构的影响，并探究其潜在机制。将16只8周龄雄性SHR随机分为两组，分别给予蒸馏水（SHR-DW）或阿托伐他汀（SHR-ATV），持续12周。以灌胃蒸馏水的年龄匹配雄性Wistar-Kyoto（WKY）大鼠作为对照。评估左心室重构情况，采用蛋白质免疫印迹法检测心肌结缔组织生长因子（CTGF）表达水平，并用TUNEL法检测心肌细胞凋亡情况。与WKY和SHR-DW组相比，阿托伐他汀治疗显著降低了SHR的收缩压；阿托伐他汀显著抑制了左心室重构，表现为左心室重量/体重比降低（SHR-ATV组：4.0±0.4 vs SHR-DW组：4.7±0.4mg/g，P<0.05）、心肌细胞直径减小（SHR-ATV组：16.2±2.8 vs SHR-DW组：19.0±1.0µm，P<0.05）以及间质纤维化减轻（SHR-ATV组：3.3±2.1 vs SHR-DW组：4.5±1.8%，P<0.05）。与WKY组相比，SHR的心肌CTGF表达显著增加，心肌细胞凋亡减少。与SHR-DW组相比，阿托伐他汀治疗显著抑制了SHR的心肌CTGF表达（SHR-ATV组：0.69±0.21 vs SHR-DW组：1.12±0.27，P<0.05），并诱导了心肌细胞凋亡（SHR-ATV组：5.2±0.6 vs SHR-DW组：1.9±0.3%，P<0.05）。结果表明，早期给予阿托伐他汀可有效预防SHR的左心室重构，抑制心肌CTGF表达和诱导心肌细胞凋亡可能是其潜在机制。
