Zhao Lian-you, Chen Yong-qing, Zheng Qiang-sun, Xue Yu-sheng, Shang Fu-jun, Li Ai-guo, Wang Bin
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Zhonghua Yi Xue Za Zhi. 2005 May 25;85(19):1344-7.
To investigate the effects of simvastatin on left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) and its possible mechanism.
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.
(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).
Simvastatin reverses LVH and myocyte phenocyte transformation in the SHRs with the possible mechanism of decreasing the expression level of PKB.
探讨辛伐他汀对自发性高血压大鼠(SHR)左心室肥厚(LVH)的影响及其可能机制。
将16只雄性SHR随机分为2组,每组8只:治疗组和SHR对照组,分别通过灌胃给予辛伐他汀或葡萄糖生理盐水,持续10周。8只Wistar-Kyoto(WKY)大鼠给予生理盐水作为正常对照组。实验前测量血压,实验开始后每周测量一次。实验结束时处死大鼠,取出心脏测量左心室重量/体重。采用RT-PCR检测心肌中利钠肽(ANP)和蛋白激酶B(PKB)的mRNA表达。采用蛋白质印迹法检测PKB的蛋白表达。
(1)SHR对照组和治疗组的收缩压分别为221 mmHg±10 mmHg和217 mmHg±8 mmHg(P>0.05),正常对照组的收缩压为126±6 mmHg,显著低于两个SHR组(均P<0.01)。(2)正常对照组、SHR治疗组和SHR对照组的LVW/BW值分别为3.04 mg/g±0.12 mg/g、3.73 mg/g±0.08 mg/g和4.10 mg/g±0.13 mg/g,任意两组间差异均有统计学意义(均P<0.01)。(3)SHR对照组、SHR治疗组和正常对照组中ANP的mRNA表达水平分别为0.44±0.33、0.27±0.03和0.17±0.33(P<0.01或P<0.05)。(4)SHR对照组、SHR治疗组和正常对照组中PKB的mRNA表达水平分别为0.45±0.05、0.32±0.03和0.19±0.02(P<0.01或P<0.05)。
辛伐他汀可逆转SHR的LVH和心肌细胞表型转化,其可能机制是降低PKB的表达水平。