辛伐他汀对高血压大鼠心肌肥厚及细胞外信号调节激酶的影响

Effect of simvastatin on myocardial hypertrophy and expression or extracellular signal-regulated Kinases in spontaneously hypertensive rats

目的探讨辛伐他汀对自发性高血压大鼠(SHR)心肌肥厚及细胞外信号调节激酶(ERK)的影响。方法将14只14周龄雄性SHR随机分成2组,每组7只;其中辛伐他汀组40mg·kg^(-1)·d^(-1)灌胃;对照组灌胃载体(0.5%羧甲基纤维素钠);共10 周。并以雄性同周龄Wistar Kyoto大鼠(WKY)作对照比较。以左心室质量与体重的比值反映心肌肥厚的程度;用Western-blot 方法检测大鼠心肌总ERK(t-ERK)、磷酸化ERK(p-ERK)以及丝裂原活化蛋白激酶磷酸酶-1(MKP-1)水平。结果SHR辛伐他汀组心肌肥厚指数明显低于SHR对照组(P<0.05)。3组大鼠t-ERK水平无显著性差异(P>0.05);辛伐他汀组心肌p-ERK和p-ERK/t-ERK比值明显低于SHR对照组(P<0.01),与WKY组接近;辛伐他汀组心肌MKP-1水平低于SHR对照组(P<0.05), 与WKY组无显著差异。结论辛伐他汀能抑制心肌肥厚,其作用机制可能与降低ERK活性有关。

OBJECTIVE To explore the effect of simvastatin on myocardial hypertrophy and the expression of extracellular signal-regulated kinases （ERK） in spontaneously hypertensive rat （SHR） .METHODS Fourteen 14-week-age SHRs were randomizedly divided into 2 groups. One group was given ig simvastatin 40 mg· kg^-1 · d^-1 for 10 weeks , while the other SHR group （control） and 7 Wistar Kyoto rats （WKY）were routinely given ig vehicle （0.5% carboxymethyl cellulose） for 10 weeks. The ratio of left ventricle weight to body weight（LVW/ BW） was measured to reflect myocardial hypertrophy. The total ERK expression （t-ERK） , phosphorylated-ERK （p-ERK） and mitogen-activated protein kinase phophatase-1 （MKP-1 ） in myocardial tissue were studied by Western-blot analysis. RESULTS The ratio of LVW/BW in SHR group with treated simvastatin decreased significantly than that in control group（ P 〈 0.05）. There was no significant difference of t-ERK expression among 3 groups（ P 〉 0.05） . The level of p-ERK and the ratio of p-ERK/t-ERK in SHR group were treated with simvastatin significantly lower than that in control group（ P 〈 0.01 ）, and similar to that in WKY group. MKP-1 expression of simvastatin group was lower than that in control group（ P 〈 0.05）. There was no significant difference in MKP-1 expression between the simvastatin group and WKY group. CONCLUSION Simvastatin can inhihit ERK activation so as to result in the regression of myocardial hypertrophy in SHR.