辛伐他汀对自发性高血压大鼠左心室肥厚的影响及与蛋白激酶B表达的关系

Effects of simvastatin on the left ventricular hypertrophy in spontaneously hypertensive rats and its relationship with the expression of protein kinase B

目的探讨辛伐他汀逆转左心室肥厚(LVH)的作用及其分子生物学机制。方法16只雄性自发性高血压大鼠(SHR)分为SHR对照组和SHR治疗组,分别给予安慰剂及辛伐他汀灌胃治疗,年龄、性别、数量配对的Wistar Kyoto(WKY)大鼠给予安慰剂治疗作为正常对照组,观察辛伐他汀对大鼠收缩压和左心室重量/体重比值(LVW/BW)的影响,采用逆转录聚合酶链反应(RT PCR)检测心肌组织心钠素mRNA表达,RT PCR和Western印迹检测心肌组织蛋白激酶B(PKB)的mRNA和蛋白表达水平。结果(1)SHR对照组和SHR治疗组大鼠的收缩压分别为221mmHg±10mmHg(1mmHg=0.133kPa)和217mmHg±8mmHg,均显著高于正常对照组大鼠(126mmHg±6mm Hg),差异有统计学意义(均P<0.01),SHR治疗组大鼠收缩压与SHR对照组相比,差异无统计学意义(P>0.05)。(2)SHR对照组大鼠的LVM/BW为4.10mg/g±0.13mg/g,明显高于正常对照组(3.04mg/g±0.12mg/g),差异有统计学意义(P<0.01),而SHR治疗组的LVM/BW(3.73mg/g±0.08mg/g)明显低于SHR对照组(P<0.01)。(3)SHR对照组大鼠心肌组织心钠素的mRNA表达水平(0.44±0.03)明显高于正常对照组(0.17±0.03),SHR治疗组心钠素的表达水平(0.27±0.03)明显低于SHR对照组(均P<0.01)。(4)SHR对照组大鼠PKB的mRNA表达水平(0.45±0.05)

Objective To investigate the effects of simvastatin on left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) and its possible mechanism. Methods Sixteen male SHRs were randomly divided into 2 equal groups: treatment group and SHR control to be given simvastatin or glucose-normal saline by oral gavage for 10 weeks. Eight Wistar-Kyoto (WKY) rats were given normal saline as normal controls. Blood pressure was measured before the experiment and then once every week after the beginning of experiment. By the end of the experiment the rats were killed and their hearts were taken out to measure the left ventricle weight/body weight. RT-PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP) and of protein kinase B (PKB) in myocardium. Western blotting was used to examine the protein expression of PKB. Results (1) The systolic blood pressure of the SHR normal control and treatment groups were 221 mm Hg±10 mm Hg and 217 mm Hg±8 mm Hg respectively (P >0.05) and the systolic pressure of the normal control group was 126±6 mm Hg, significantly lower than those of the 2 SHR groups (both P<0.01). (2) The LVW/BW values of the SHR control group were 3.04 mg/g±0.12 mg/g, 3.73 mg/g±0.08 mg/g, and 4.10 mg/g±0.13 mg/g in the normal control group, SHR treatment group and SHR control group respectively with significant difference between any 2 groups (all P<0.01). (3) The mRNA expression levels of ANP were 0.44±0.33, 0.27±0.03, and 0.17±0.33 in the SHR control group, SHR treatment group, and normal control group respectively (P<0.01 or P<0.05). (4) The mRNA expression levels of PKB were 0.45±0.05, 0.32±0.03, and 0.19±0.02 in the SHR control group, SHR treatment group, and normal control group respectively (P<0.01 or P<0.05). Conclusion^Simvastatin reverses LVH and myocyte phenocyte transformation in the SHRs with the possible mechanism of decreasing the expression level of PKB.