阿托伐他汀逆转自发性高血压大鼠左室重塑的效应及机制

目的:观察阿托伐他汀对自发性高血压大鼠(SHR)左室重塑的影响并探讨其可能的机制。方法:将10只8周龄的SHR随机分为蒸馏水饲养组(SHRDW组,n=5)和阿托伐他汀治疗组(SHRATV组,n=5),并以5只同周龄的正常血压大鼠(WKY)作为对照(WKY组,n=5)。10周后分别采用TUNEL法和免疫组化法检测左室心肌细胞的凋亡及P27蛋白的表达,比色法测定心肌组织羟脯氨酸的含量,计算左室重与体重比,检测血压和血脂。结果:阿托伐他汀干预10周后,SHRATV组左室重、左室重与体重比,以及心肌组织羟脯氨酸含量均明显低于SHRDW组(P<0.01),左室心肌细胞的凋亡率及P27蛋白的阳性表达率比SHRDW组明显增加(P<0.01);此外,SHRATV组收缩压水平与治疗前和SHRDW组相比显著降低(P<0.01),其血清脂质水平与SHRDW组及WKY组相比也明显下降(P<0.01)。结论:阿托伐他汀能够逆转SHR左室重塑,其机制可能与阿托伐他汀促进心肌细胞的凋亡、上调心肌细胞P27蛋白的表达,以及降低心肌组织羟脯氨酸的含量有关。

Effect of atorvastatin on left ventricular remodeling in spontaneously hypertensive rats

Objective: To observe the effect of atorvastatin on left ventricular remodeling in spontaneously hypertensive rats(SHR),and to explore its possible mechanism involved.Methods: Ten eight-week-old SHR were randomized into distilled water group(SHR_(DW) group,n=5) and atorvastatin treated group(SHR_(ATV) group,n=5);the age-matched wistar-kyoto rats(WKY)were used as controls(WKYgroup,n=5).TUNEL technology and immunohistochemistry method were respectively used to detect the apoptotic rate and P27 protein expression in cardiomyocytes.Colorimetric method was used to measure myocardial hydroxyproline(Hyp) content.Meanwhile,left ventricular weight to body weight ratio(LVW/BW),systolic blood pressure(SBP) and serum lipids levels were examined.Results: After 10 weeks treatment with atorvastatin,LVW/BW ratio and myocardial Hyp content in SHR_(ATV) group were markedly decreased compared to SHR_(DW) group(P<0.01);the apoptotic rate and P27 protein expression in cardiomyocytes in SHR_(ATV) group were much higher than those in SHR_(DW) group(P<0.01).In addition,compared with before treatment and SHR_(DW) group,SBP in SHR_(ATV) group was markedly decreased(P<0.01).The serum lipids levels in SHR_(ATV) group were also markedly lower than those in SHR_(DW) group and WKY group(P<0.01).Conclusion: Administration of atorvastatin can prevent left ventricular remodeling in SHR,and the possible mechanism involved might be associated with its ability to facilitate cardiomyocytes apoptosis,upregulate P27 protein expression and reduce myocardial Hyp content.