【摘要】 目的研究Rho激酶抑制剂法舒地尔(fasudil)对大鼠腹主动脉缩窄压力超负荷诱导的心肌肥厚的影响及机制。方法50只雄性Wistar大鼠随机分为5组:假手术组、压力超负荷模型组、法舒地尔低剂量组、法舒地尔高剂量组及阳性对照(卡托普利)组,每组10只。除假手术组外,其他4组大鼠结扎肾上方腹主动脉制备压力超负荷模型,4周后建立心肌肥厚模型并开始给药,疗程4周。给药结束后,检测各组血流动力学指标,心脏重量指数(HW/BW)及左心室重量指数(LVW/BW);取心肌组织,经不同染色方法,观察心肌病理改变并检测心肌细胞直径(MD)和心肌胶原百分比(CVF);RT-PCR法检测心肌组织中RhoA、Rho激酶mRNA的表达。结果与假手术组比较,模型组的LVEDP明显增加,LVSP明显下降;HW/BW、LVW/BW明显增加;MD增大(P<0.01),CVF明显增加(P<0.05);RhoA、Rho激酶mRNA的表达明显上调(均P<0.01)。与模型组比较,经法舒地尔及阳性药物治疗后,上述指标均有不同程度的改善(均P<0.05,P<0.01)。结论Rho激酶抑制剂法舒地尔可以改善心功能,抑制心肌胶原的合成及心肌纤维化,改善压力超负荷所引起的心肌肥厚。更多还原

【Abstract】 Objective To explore the effect of Rho kinase inhibitor fasudil on the pressure overload induced cardiac hypertrophy(POH) in rats and the mechanism involved.Methods The POH model was established by constriction of the supra-renal abdominal aorta.4 weeks after operation,POH rats were randomly divided into 4 groups(n=10 each group): fasudil 1 or 5 mg/kg bid,captopril 30 mg·kg-1·d-1 or vehicle treatment for 4 weeks.Sham animals(n=10) underwent surgery without banding and they received vehicle treatment for 4 weeks.At the completion of the study,body weights(BW) and haemodynamic parameters were obtained.The hearts were harvested and heart weights(HW) and left ventricle weights(LVW) were recorded to calculate the ratios of HW/BW and LVW/BW.The pathological changes of myocardium stained with HE or Masson were examined,myocardial diameter(MD) and collagen volume fraction(CVF) of the myocardium were measured.The expressions of RhoA and Rho kinase were examined by RT-PCR.Results LVEDP of the POH group was increased but LVSP was decreased compared with that of sham group.HW/BW and LVW/BW of POH group were higher than those of sham group.CVF was increased in POH group compared with that in sham group.The mRNA expression levels of RhoA and Rho kinase in POH group were higher than those of sham group.Compared with the POH group,LVSP of fasudil groups was increased at different degrees,while LVEDP,HW/BW,LVW/BW,mRNA of RhoA and Rho kinase in fasudil groups were lower than those of sham group.Conclusions Rho kinase inhibitor fasudil could effectively protect cardiac function and attenuate collagen synthesis and cardiac fibrosis,therefore improve left ventricular remodeling and cardiac hypertrophy in POH rats.更多还原