阿托伐他汀影响自发性高血压左室肥厚的实验研究

目的研究阿托伐他汀对自发性高血压大鼠肥厚心肌过氧化物酶体增殖物激活受体γ(PPARγ)及p21表达的影响,了解阿托伐他汀改善左室肥厚的可能机制.方法筛选8周龄同批次自发性高血压大鼠20只作为研究对象,将其随机分为空白组和观察组,每组10只,另选8周龄同批次健康大鼠作为对照组,3组大鼠的体质量、周龄、雌雄比例比较无统计学意义.空白组和健康对照组大鼠采用蒸馏水灌胃,观察组大鼠采用剂量50 mg/(kg·d-1)的阿托伐他汀灌胃,所有实验大鼠每5周测1次血压,10周后测量大鼠的血脂水平、心肌肥厚,采用免疫组化及RT-PCR观察PPARγ和p21的表达,并进行3组比较.结果 10周后,观察组大鼠的心肌肥厚指标明显低于空白组(P0.01);PPARγ和p21的表达明显高于空白组(P0.01);心肌组织PPARγ和p21 mRNA的表达呈负相关.结论阿托伐他汀通过上调自发性高血压大鼠肥厚心肌组织中PPARγ,p21的表达来调节细胞周期,可有效改善高血压左室肥厚.

Laboratory Study on the Influence of Atorvastatin on Left Ventricular Hypertrophy in Spontaneously Hypertensive

Objective To study the influence of atorvastatin on the expressions of peroxisome proliferator-activated receptor γ ( PPARγ) and p21 in the hypertrophic myocardium in spontaneously hypertensive rats,and to understand the mechanisms of atorvastatin in improving left ventricular hypertrophy. Method Thirty spontaneously hypertensive rats of 8-week-old within the same batch were randomly divided into blank group, observation group and control group,10 rats in each group. The weight,week-old,male and female ratio were not statistically significant among three groups. The blank group and the healthy control group were given distilled water,and the observation group was administrated 50 mg/( kg · d-1 ) dose of atorvastatin by gavage. Blood pressures of all the rats were measured every five weeks,serum lipid levels and the thicknesses of myocardium were tested after 10 weeks. The immunohistochemistry method and RT-PCR were performed to observe the expression of PPARγ and p21. Results After 10 weeks,the cardiac hypertrophy index of the observation group was significantly lower than that of the control group (P<0. 01),the expressions of PPARγ and p21 in the
observation group was significantly higher than those in the control group ( P<0 . 01 ) , and the expressions of PPARγ and p21 mRNA in myocardial tissue showed a negative correlation. Conclusion Atorvastatin can regulate the cell cycle by increasing the expressions of PPARγ and p21 in the hypertrophic myocardium in spontaneously hypertensive rats,and thus improve left ventricular hypertrophy.