[Rho激酶抑制剂对自发性高血压大鼠左心室心肌肥厚的影响]
[Effects of rho-kinase inhibitor on cardiac hypertrophy of left ventricle in spontaneously hypertensive rats].
作者信息
Zhang Zhi-jie, Fan Yan-fu, Zhang Zhi-ying, Xie Pei-yi, Fang Hong-cheng, Su You-su
机构信息
Department of Cardiology, Guangdong Medical College, Shenzhen, China.
出版信息
Zhonghua Yi Xue Za Zhi. 2012 Dec 25;92(48):3438-41.
OBJECTIVE
To explore the effects of Rho-kinase inhibitor on cardiac hypertrophy of left ventricle in spontaneously hypertensive rats (SHR).
METHODS
SHRs (n = 30) were randomly divided into 5 groups (n = 6 each): SHR control group, 5 mg/kg fasudil group (SHRL), 10 mg/kg fasudil group (SHRM), 20 mg/kg fasudil group (SHRH) and nifedipine group (XBDP, 10 mg/kg). Six male Wistar-Kyoto rats were selected as normal control group (WKY group). Systolic blood pressure (SBP) was measured before and after treatment every 2 weeks. The hypertrophic parameters of left ventricular weight index (LVWI) and cardiomyocyte transverse diameter (TDM) were measured. In addition, the expression levels of Rho kinase mRNA and protein in cardiomyocytes were observed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.
RESULTS
The levels of LVWI and TDM in WKY group were significantly lower than those in SHR control group [(2.98 ± 0.05) vs (3.16 ± 0.08) mg/g, (18.18 ± 0.75) vs (21.32 ± 1.25) µm, P < 0.01]. After 8 weeks, the levels of LVWI and TDM in three fasudil groups were markedly lower than those in SHR control group [SHRL group: (3.12 ± 0.05) mg/g, SHRM group: (3.10 ± 0.07) mg/g, SHRH group: (3.08 ± 0.09) mg/g vs SHR control group: (3.16 ± 0.08) mg/g, SHRL group: (20.11 ± 1.15) µm, SHRM group: (19.63 ± 1.62) µm, SHRH group: (18.91 ± 1.05) µm vs SHR control group: (21.32 ± 1.25) µm, P < 0.05 or P < 0.01]. But the levels of LVWI and TDM were not different between SHR control and XBDP groups [(3.14 ± 0.08) mg/g,(21.42 ± 1.23) µm, P > 0.05]. Compared with SHR control group, the expression of Rho kinase mRNA and protein in cardiomyocytes significantly decreased in three fasudil groups [SHRL group mRNA: (0.45 ± 0.08), SHRM group mRNA: (0.37 ± 0.07), SHRH group mRNA: (0.32 ± 0.07) vs SHR control group mRNA: (0.63 ± 0.07), SHRL group protein: 0.78 ± 0.11), SHRM group protein: (0.73 ± 0.10), SHRH group protein: (0.68 ± 0.10) vs SHR control group protein: (0.90 ± 0.1), P < 0.05 or P < 0.01], but showed no obvious change in XBDP group [mRNA: (0.56 ± 0.07), protein: (0.85 ± 0.10), P > 0.05].
CONCLUSIONS
Rho kinase inhibitor may significantly down-regulate the expression of Rho kinase in cardiomyocytes of SHR. The mechanism is probably due to the favorable effects of Rho kinase inhibitor in the prevention of cardiac hypertrophy of left ventricle.
目的
探讨Rho激酶抑制剂对自发性高血压大鼠（SHR）左心室心肌肥厚的影响。
方法
将30只SHR随机分为5组（每组6只）：SHR对照组、5mg/kg法舒地尔组（SHRL）、10mg/kg法舒地尔组（SHRM）、20mg/kg法舒地尔组（SHRH）和硝苯地平组（XBDP，10mg/kg）。选取6只雄性Wistar-Kyoto大鼠作为正常对照组（WKY组）。每2周测量治疗前后的收缩压（SBP）。测量左心室重量指数（LVWI）和心肌细胞横径（TDM）等肥厚参数。此外，通过逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法观察心肌细胞中Rho激酶mRNA和蛋白的表达水平。
结果
WKY组的LVWI和TDM水平显著低于SHR对照组[（2.98±0.05）对（3.16±0.08）mg/g，（18.18±0.75）对（21.32±1.25）µm，P<0.01]。8周后，3个法舒地尔组的LVWI和TDM水平均显著低于SHR对照组[SHRL组：（3.12±0.05）mg/g，SHRM组：（3.10±0.07）mg/g，SHRH组：（3.08±0.09）mg/g对SHR对照组：（3.16±0.08）mg/g，SHRL组：（20.11±1.15）µm，SHRM组：（19.63±1.62）µm，SHRH组：（18.91±1.05）µm对SHR对照组：（21.32±1.25）µm，P<0.05或P<0.01]。但SHR对照组和XBDP组的LVWI和TDM水平无差异[（3.14±0.08）mg/g，（21.42±1.23）µm，P>0.05]。与SHR对照组相比，3个法舒地尔组心肌细胞中Rho激酶mRNA和蛋白的表达显著降低[SHRL组mRNA：（0.45±0.08），SHRM组mRNA：（0.37±0.07），SHRH组mRNA：（0.32±0.07）对SHR对照组mRNA：（0.63±0.07），SHRL组蛋白：0.78±0.11），SHRM组蛋白：（0.73±0.10），SHRH组蛋白：（0.68±0.10）对SHR对照组蛋白：（0.90±0.1），P<0.05或P<0.01]，而XBDP组无明显变化[mRNA：（0.56±0.07），蛋白：（0.85±0.10），P>0.05]。
结论
Rho激酶抑制剂可能显著下调SHR心肌细胞中Rho激酶的表达。其机制可能是Rho激酶抑制剂对预防左心室心肌肥厚具有有益作用。
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