阿托伐他汀对压力负荷引起高血压大鼠心肌肌浆网钙泵活力的影响  

Effect of Atorvastatin on Activity of Myocardial Sarcoplasmic Reticulum Calcium Pump in Pressure-loaded Hypertensive Rats

作　　者：何世保[1] 王安才[1] 陈月云[1] 汪俊元[1] 汪念东[1] 

机构地区：[1]皖南医学院弋矶山医院老年医学科,安徽芜湖241000

出　　处：《中华高血压杂志》2010年第2期160-164,共5页Chinese Journal of Hypertension

基　　金：皖南医学院博士基金项目(2005021);皖南医学院青年基金项目(WK200810F)

摘　　要：目的观察阿托伐他汀对压力负荷增高所致左心室肥厚(LVH)和心肌肌浆网钙泵(SERCA)活力的影响。方法雄性SD大鼠50只随机分为假手术组、腹主动脉缩窄(AAC)组、阿托伐他汀10mg/(kg·d)(Ato10mg)、阿托伐他汀30mg/(kg·d)(Ato30mg)和氨氯地平5mg/(kg·d)组,每组10只。采用腹主动脉缩窄术建立LVH动物模型,灌胃法给药4周。鼠尾容积法测量收缩压,计算左心室质量指数(LVMI),即左心室质量/体质量(LVM/BM);HE染色检测心肌细胞平均直径;无极磷酸根法测定SERCA活力;双波长荧光分光光度计检测心肌细胞内Ca2+浓度。结果与假手术组相比,AAC组收缩压、LVMI、心肌细胞平均直径、细胞内Ca2+浓度均显著升高,心肌SERCA活力(4.0±0.6)比假手术组(6.4±0.8)μmol/(mgpro.h)明显降低(均P<0.05)。与AAC组比较,阿托伐他汀30mg组及氨氯地平组均能降低大鼠收缩压、LVMI、心肌细胞平均直径和细胞内Ca2+浓度,同时能明显提高心肌SERCA活力[Ato30mg组(4.9±0.4),氨氯地平组(4.8±0.5)比AAC组(4.0±0.6)μmol/(mgpro·h),均P<0.05]。结论阿托伐他汀改善腹主动脉缩窄高血压大鼠LVH可能与增加SERCA活力,降低压力负荷诱导的肥厚心肌细胞中Ca2+浓度有关。Objective To investigate the effect of atorvastatin on left ventricular hypertrophy induced by pressure overload and the activity of myocardial sarcoplasmic reticulum calcium（SERCA）.Methods Left ventricular hypertrophy was induced by abdominal aortic constriction（AAC） in adult SD rats, and received atorvastatin 10 mg/（kg·d）（n=10）, atorvastatin 30 mg/（kg·d）（n=10）, amlodipine group（5 mg/kg·d）（n=10）.Sham operated rats（n=10） and untreated AAC rats（n=10） served as controls.Systolic blood pressure （SBP） and LVMI were determined, cardiomyocytes diameter were measured by HE stain; the activity of myocardial SERCA was determined by non-polar phosphate method; Ca2＋ concentration in cardiomyocytes was detected by dual wave spectrofluorometer.ResultsCompared with sham operation group, SBP, LVMI, mean diameter of cardiomyocytes and Ca2＋ concentration of cardiomyocytes in AAC rats were significantly increased; while the activity of myocardium SERCA （4.0±0.6） vs （6.4±0.8） μmol/（mg pro·h） was significantly decreased （all P〈0.05）.SBP, LVMI, mean diameter of cardiomyocytes and Ca2＋ concentration of cardiomyocytes in AAC rats were significantly decreased in both atorvastatin 30 mg/（kg·d） and amlodipine group. The activity of myocardium SERCA [Ato 30 mg （4.9±0.4）, amlodipine （4.8±0.5） vs AAC（4.0±0.6） μmol/（mg pro·h）, all P〈0.05] was significantly increased in atorvastatin and amlodipine treated groups.ConclusionHigh dose of atorvastatin could prevent AAC induced left ventricular hypertrophy, possibly via increaing the activity of myocardial SERCA and reducing Ca2＋ concentration in hypertrophic myocardial cells.

关 键 词：阿托伐他汀 高血压 左心室肥厚 肌浆网钙泵 大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]