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

 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。

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

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 inhibit ERK activation so as to result in the regression of myocardial hypertrophy in SHR.