阿托伐他汀对自发性高血压大鼠左室肥厚的影响及其可能机制

Effects and its Underlying Mechanism of Atorvastatin on Spontaneously Hypertensive rats with Left Ventricular Hypertrophy

目的应用阿托伐他汀抑制自发性高血压大鼠出现左室肥厚心肌过氧化物酶体增殖物激活受体γ(PPARγ)和p21表达及其改善机制。方法随机将同批次16只具有8周龄的自发性高血压大鼠分为阿托伐他汀ATV组与自发性高血压SHR组(各8只);另选取8只同周龄大鼠作为正常血压WKY组。采用阿托伐他汀对ATV组进行灌胃,50 mg/(kg·d);对SHR组与WKY组进行等容量蒸馏水灌胃,测量3组大鼠血压,5周/次;持续干预10周后,对其血压及血脂水平进行观察与测量,同时计算其心肌肥厚指标,并使用RT-PCR、免疫组化观察PPARγ和p21的表达。结果血脂及血压观测结果显示,SHR组与ATV组无显著差异,ATV组心肌肥厚指标明显低于SHR组,差异有统计学意义(P<0.01);ATV组PPARγ和p21的表达明显高于SHR组,差异有统计学意义(P<0.01)。心肌组织PPARγ和p21 m RNA的表达表现出负相关性。结论阿托伐他汀可自行对自发性高血压大鼠心肌细胞中PPARγ、p21上调以对细胞周期进行调节,对高血压左室肥厚具有改善作用。

Objective To investigate the effect of atorvastatin on peroxisome proliferator-activated receptor-γ（PPARγ） and p21 expression of hypertrophic myocardium in spontaneously hypertensive rats and discuss the underlying mechanisms which atorvastatin improves left ventricular hypertrophy. Methods 16 eight-week-old male spontaneously hypertensive rats were randomly divided into atorvastatin group（ATV group, n=8） and spontaneously hypertensive rats group（SHR group, n=8）. Age –matched Wistar- kyoto rats were served as normal blood pressure control group（WKY group, n=8）. In ATV group, atorvastatin was given at a dose of 50 mg/（kg·d） perday by gastric gavage, and in SHR and WKY group, the same volume of distilled water by gavage. Measure the blood pressure every five weeks. Ten weeks later, blood pressure and plasma lipid levels were measured. The ratio of the heart weight to body weight（HW/BW） and the left ventricular weight to body weight（LVW/BW） were calculated as myocardial hypertrophy index. The expressions of PPARγ and p21 were investigated by the method of immunohistochemistry analysis and RT-PCR. Results There was not much difference of plasma lipid levels and blood pressure between ATV and SHR group. Compared with SHR group, Myocardial hypertrophy index decreased significantly in ATV group（P〈0.01）. The myocardium PPARγ and p21 expression increased significantly（P〈0.01）. The association between expression of PPARγm RNA and p21 m RNA in cardiomyocytes and myocardial hypertrophy index are negative correlation. Conclusion Atorvastatin increases myocardium PPARγ and P21 expression and improves left ventricular hypertrophy in spontaneously hypertensive rats.