压力负荷心力衰竭大鼠心肌细胞内Rho/Rho激酶的表达及药物干预

目的探讨升主动脉缩窄压力超负荷心力衰竭大鼠心肌细胞内Rho／Rho激酶的表达及法舒地尔(fasudil)——Rho／Rho激酶拮抗剂对心力衰竭的影响。方法制备升主动脉缩窄大鼠心力衰竭及假手术组(S组)模型。将升主动脉缩窄术后Wistar雌性大鼠随机分为2组，一组为心力衰竭组(H组)，给予生理盐水0．1ml。腹腔注射，每日2次：一组为fasudil治疗组(F组)，治疗组给予fasudil 5mg／Kg，腹腔注射，每日2次；治疗4周。H组、F组及S组每组各10只大鼠。观察各组大鼠各项指标变化。结果H组鼠心肌细胞RhoA，Rho激酶mRNA表达显著增高，F组心肌细胞RhoA mRNA，Rho激酶mRNA表达下降。结论心肌细胞RhoA、Rho激酶表达与充血性心力衰竭密切相关，法舒地尔可有效降低心肌细胞内RhoA mRNA，Rho激酶mRNA表达，缓解心力衰竭症状，可能为一种新的、有效的治疗心力衰竭的血管扩张剂。

Expression of Rho/Rho kinase of cardiac myocyte of heart failure model of pressure overload rats and intervention of fasudil

Objective: To study the expression of Rho/Rho kinase of cardiac myocyte of heart failure pressure overload rat models subsequent to coarctation of ascending aorta and the effects of fasudil on heart failure. Methods: A model of heart failure induced by coarctation of ascending aorta was used in this study. 20 female wistar operation rats were divided randomly into two groups (n =10). Heart failure (Natrii chloridi, 0.1 ml), fasudil (5 mg/Kg), Bid i.p, 20 weeks after coarctation of ascending aorta operation, 10 agematched sham operation group as control. Treatment time was 4 weeks. Hemodynamics, ratio of LV weight to body weight, expression of RhoA and Rho kinase mRNA were investigated in the two groups and sham operation group. Results: RhoA, Rho kinase mRNA level were higher in heart failure when compared with sham. Fasudil could change the expression of RhoA, Rho kinase mRNA level. Conclusion: These results indicate that heart failure is probably related to activating of RhoA, Rho kinase. Fasudil may contribute to the observed beneficial effects on heart failure by the decrease of RhoA, Rho kinase mRNA expression. Fasudil may be a novel, potent vasodilator for the treatment of heart failure.