摘要
目的研究阿托伐他汀(Ato)对自发性高血压大鼠(SHR)心室重构的作用,并探讨其作用机制。方法16周龄雄性SHR40只,随机分为4组,即SHR组、阿托伐他汀10mg组(Ato-1组)、25mg组(Ato-2组)和50mg组(Ato-3组)。Wistar-Kyoto(WKY)大鼠10只作为正常对照组(WKY组)。Ato-1组、Ato-2组和Ato-3组每日分别用阿托伐他汀10、25、50mg/kg灌胃。实验8周后,测定血液动力学指标,左室质量指数(LVMI),RT-PCR检测心肌转化生长因子β1(TGFβ1) mRNA、Smad3 mRNA和Smad7 mRNA。结果SHR组心室功能障碍,LVMI明显增高[(3.20±0.21)mg/g比WKY:(2.10±0.14)mg/g](P<0.01),心肌TGFβ1 mRNA(125.4±3.2比WKY:73.6±2.1,P<0.01)、Smad3 mRNA(6.40±0.43比WKY:3.10±0.75,P<0.01)增加,心肌Smad7 mRNA(2.30±0.86比WKY:4.10±1.23,P<0.01)降低。Ato呈剂量依赖性改善左室功能,降低SHRLVMI,降低心肌TGFβ1 mRNA、Smad3 mRNA,增加心肌Smad7 mRNA。结论阿托伐他汀可能通过下调心肌TGFβ1 mRNA、Smad3 mRNA和上调心肌Smad7 mRNA,改善SHR心室重构。
Objective The effect of atorvastatin on amelioration of ventricular remodel has been reported but the mechanism is not certain. This paper aimed to explore the mechanism by which atorvastatin（Ato） inhibites myocardial remodeling in spontaneously hypertensive rat （SHR）. Methods Thirty 16-week old SHR were orally treated with different doses of Ato （10, 25 and 50 mg/kg） for 8 weeks. Untreated SHR（ n= 10） and WKY（ n= 10） rats were used as controls. The cardiac functions were determined in vivo at the end of the experiments and left ventricular mass index was calculated. The mRNA levels of transforming growth factor-β1 （ TGF-β1 ） and smad 3 and 7 subtypes in myocardial tissues were determined using RT-PCR. Results Significant deterioration in cardiac function and increase in left ventricular mass index in SHR（3. 20±0.21 mg/g） compared with those of WKY（ 2. 10±0. 14 mg/g, P〈0. 01 ） were found. Furthermore, the level of TGF-β1 mRNA in myocardial tissues of SHR was significantly increased（SHR：125.4±3.2 vs WKY：73.6±2. 1）, with increase in level of Smad 3 mRNA （SHR：6.40±0. 43 vs WKY：3. 10±0.75, P〈0.01） and decrease in level of Smad 7 mRNA（SHR：2. 30± 0. 86 vs WKY：4.10±1. 23, P〈0.01）. Oral treatment with Ato for 8 weeks dose-dependently improve cardiac function and decrease left ventricular mass index. Moreover, atorvastatin markedly downregulate the levels of both TGF-β1 and Smad 3 and upregulate the level of Smad 7 mRNA. Conclusion Ato exert an inhibitory effect on myocardial remodeling in SHR, and such effect of Ato may be related to regulating TGF-β1/Smad signaling pathway.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2007年第6期497-500,共4页
Chinese Journal of Hypertension
