阿托伐他汀对自发性高血压大鼠心室重构的影响

Effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats

目的 :观察阿托伐他汀对自发性高血压大鼠(SHR)心室重构的影响。方法 :2 4只SHR随机分为4组 ,每组 6只。SHR对照组、阿托伐他汀 5 0mg组(5 0mg·kg-1·d-1)、阿托伐他汀 10mg组(10mg·kg-1·d-1)和缬沙坦组 (2 0mg·kg-1·d-1) ;6只Wistar Kyoto大鼠 (WKY)作为正常对照组。灌胃给药共 6周 ,分别于给药前和给药后每 2周测量大鼠尾动脉收缩压 (SBP)。酶法测定血清总胆固醇(TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)及低密度脂蛋白胆固醇 (LDL C)含量 ,放免法测定血浆和心肌血管紧张素Ⅱ (AngⅡ )水平 ,并检测心肌羟脯氨酸、胶原蛋白含量和全心重量 (HW )、左室重量 (LVM )及左室重量指数 (LVMI)。透射电镜观察心肌超微结构改变。结果 :用药前SHR各组SBP均显著高于WKY正常对照组 (P <0 .0 1) ,给药后第 4、6周 ,阿托伐他汀 5 0mg组SBP明显下降 (P <0 .0 1) ,阿托伐他汀 10mg组不明显 ;缬沙坦组自给药后第 2周 ,SBP明显下降 (P <0 .0 1)。阿托伐他汀5 0mg组TC、TG及LDL C水平较SHR对照组明显降低 (P <0 .0 5或P <0 .0 1) ,阿托伐他汀 10mg组仅LDL C水平明显下降 (P <0 .0 5 )。SHR对照组血浆AngⅡ浓度与WKY正常对照组比较无显著性差异 ,但心肌AngⅡ浓度明显增高 (P <0 .0 5 ) ;给药 6周后 ,阿托伐他?

AIM: To investigate the effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats (SHR). METHODS: SHRs (n=24) were randomly divided into four groups (n=6): SHR control group, 50 mg atorvastatin group (50 mg·kg -1·d -1), 10 mg atorvastatin group (10 mg·kg -1·d -1) and valsartan group (20 mg·kg -1·d -1). Six male Wistar-Kyoto rats were selected as normal control group (WKY group). Systolic blood pressure (SBP) was measured before and after treatment with atorvastatin every 2 weeks. Plasma concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Ang, and myocardial AngⅡ, hydroxyproline and collagen levels were measured. Heart weight (HW), left ventricle mass (LVM) and left ventricle mass index (LVMI) were gauged. Myocardial ultrastructure was observed by transmission electron microscopy. RESULTS: SBP in all SHR groups was much higher than that in WKY group before experiment (P< 0.01). SBP significantly decreased in 50 mg atorvastatin group at 4 weeks and 6 weeks (P< 0.01). Compared with SHR control group, there was a significant descent in serum TC, TG and LDL-C concentrations in 50 mg atorvastatin group (P< 0.05, or P< 0.01). The level of LDL-C decreased merely in 10 mg atorvastatin group (P< 0.05). There was no difference in plasma Ang Ⅱ level among WKY group and SHR groups. But myocardial Ang Ⅱ level in SHR group was significantly higher than that in WKY group (P< 0.05). After 6 weeks, plasma AngⅡ level among atorvastatin groups and valsartan group was markedly higher than that in SHR control group (P< 0.01), and myocardial AngⅡ level was significantly lower than that in SHR group (P< 0.05). Myocardial hydroxyproline and collagen level in SHR group was significantly higher than that in WKY group (P< 0.01). After treatment of 50 mg atorvastatin, it was markedly lower than that in SHR control group (P< 0.05). Compared with WKY group, HW,LVM and LVMI were significantly increased in SHR group (P< 0.01). After treatment of 50 mg atorvastatin, HW,LVM and LVMI were significantly lower than those in SHR control group (P< 0.05). The changes of myocardial ultrastructure in atorvastatin and valsartan groups were significantly improved. CONCLUSION: Atorvastatin can significantly improve ventricular remodeling in SHR, and decrease blood pressure and myocardial Ang Ⅱ level which may be one of its mechanisms.