[压力超负荷致心力衰竭大鼠心肌中Rho/Rho激酶的表达及法舒地尔的干预作用]
[The expression of Rho/Rho kinase of cardiac muscle in heart failure rats caused by pressure overload and the intervention of fasudil].
作者信息
Zhang Man, Qu Chen, Zeng Ding-yin
机构信息
Department of Cardiology, Affiliated Central Hospital, Shenyang Medical College, Shenyang 110024, China.
出版信息
Zhonghua Xin Xue Guan Bing Za Zhi. 2005 Jan;33(1):73-6.
OBJECTIVE
To study the expression of Rho/Rho kinase of cardiac muscle in heart failure rats caused by pressure overload and the effects of fasudil on heart failure.
METHODS
The heart failure models were successfully induced by coarctation of ascending aorta after 20 weeks in this study. Thirty female Wistar operated rats were divided randomly into three groups (n = 10) for 4 week treatment. (1) Sham operation group: normal saline, 0.1 ml, i.p,Bid. (2) Heart failure group: normal saline, 0.1 ml,i.p,Bid. (3) Fasudil group: fasudil 5 mg/kg, i.p, Bid. The hemodynamic parameters, the ratio of LV weight to body weight, the expressions of RhoA and Rho kinase mRNA, and the concentration of calcium ion same as Ca(2+) were investigated in the three groups.
RESULTS
Hemodynamic parameters were significantly changed in heart failure group than those in sham operation group, such as left ventricular diastolic end pressure increased [(13.00 +/- 0.30) mm Hg vs (3.78 +/- 0.31) mm Hg, P < 0.01], left ventricular systolic pressure decreased [(97.20 +/- 7.21) mm Hg vs (129.45 +/- 7.52) mm Hg, P < 0.01]. Those results could be significantly changed by use of fasudil, P < 0.01. The ratio of LV weight to body weight was significantly increased in heart failure group than that in sham operation group [(4.77 +/- 0.08) mg/g vs (2.51 +/- 0.12) mg/g, P < 0.01]. Fasudil could significantly decrease the ratio of LV weight to body weight compared with that in heart failure group [(4.05 +/- 0.08) mg/g vs (4.77 +/- 0.08) mg/g, P < 0.01]. Cardiac muscle RhoA, Rho kinase mRNA level and Ca(2+) were higher in heart failure group than those in sham operation group Ca(2+) (475.93 +/- 28.22) nmol/L vs (79.25 +/- 3.33) nmol/L, P < 0.01. Compared with those in heart failure group, the expressions of RhoA, Rho kinase mRNA level decreased significantly, P < 0.01, and the levels of cardiomyocyte Ca(2+) had no change in fasudil group [(462.78 +/- 16.72) nmol/L vs (475.93 +/- 28.22) nmol/L, P > 0.05].
CONCLUSIONS
These results indicated that heart failure was probably related to activating of RhoA, Rho kinase. Fasudil may contribute to the observed beneficial effects on heart failure such as the decrease of RhoA, Rho kinase mRNA expression and not increase of Ca(2+) level. Rho/Rho kinase may be a novel, potent signaling of heart failure.
目的
研究压力超负荷致心力衰竭大鼠心肌中Rho/Rho激酶的表达及法舒地尔对心力衰竭的影响。
方法
本研究中，升主动脉缩窄20周后成功诱导出心力衰竭模型。30只接受手术的雌性Wistar大鼠随机分为三组（n = 10），进行为期4周的治疗。（1）假手术组：腹腔注射生理盐水0.1 ml，每日2次。（2）心力衰竭组：腹腔注射生理盐水0.1 ml，每日2次。（3）法舒地尔组：腹腔注射法舒地尔5 mg/kg，每日2次。观察三组的血流动力学参数、左心室重量与体重比值、RhoA和Rho激酶mRNA的表达以及钙离子浓度Ca(2+)。
结果
心力衰竭组的血流动力学参数与假手术组相比有显著变化，如左心室舒张末压升高[（13.00±0.30）mmHg对（3.78±0.31）mmHg，P < 0.01]，左心室收缩压降低[（97.20±7.21）mmHg对（129.45±7.52）mmHg，P < 0.01]。使用法舒地尔可使这些结果发生显著变化，P < 0.01。心力衰竭组的左心室重量与体重比值显著高于假手术组[（4.77±0.08）mg/g对（2.51±0.12）mg/g，P < 0.01]。与心力衰竭组相比，法舒地尔可显著降低左心室重量与体重比值[（4.05±0.08）mg/g对（4.77±0.08）mg/g，P < 0.01]。心力衰竭组心肌RhoA、Rho激酶mRNA水平和Ca(2+)高于假手术组Ca(2+)（475.93±28.22）nmol/L对（79.25±3.33）nmol/L，P < 0.01]。与心力衰竭组相比，法舒地尔组RhoA、Rho激酶mRNA水平显著降低，P < 0.01，心肌细胞Ca(2+)水平无变化[（462.78±16.72）nmol/L对（475.93±28.22）nmol/L，P > 0.05]。
结论
这些结果表明，心力衰竭可能与RhoA、Rho激酶的激活有关。法舒地尔可能对心力衰竭具有有益作用，如降低RhoA、Rho激酶mRNA表达且不增加Ca(2+)水平。Rho/Rho激酶可能是心力衰竭的一种新的重要信号通路。
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