【摘要】 目的研究Rho激酶抑制剂对异丙肾上腺素(isoproterenol,Iso)诱导大鼠心肌肥厚的影响及其机制。方法40只雄性Wistar大鼠随机分为5组:空白对照组、Iso模型组、法舒地尔(fasudil,Fas)低剂量组、高剂量组及卡托普利(captopril,Cap)组,每组8只。除空白对照组外,各组皮下注射Iso建立大鼠心肌肥厚模型。给药结束后分别测定各组大鼠体重(BW)、心脏重量(HW),计算心脏重量指数(HW/BW);测定左室收缩压(LVSP)、左室舒张末压(LVEDP)、左心室压力上升及下降最大速率(±dp/dtmax)等指标;取心肌组织作病理学检测;RT-PCR测定心肌组织RhoA、Rho激酶mRNA表达。结果Iso模型组大鼠HW/BW增大;LVEDP增加,而LVSP、±dp/dtmax下降;心肌细胞直径增大、胶原纤维增生;左心室组织RhoA、Rho激酶mRNA表达上调。使用Fas和Cap干预,上述指标均出现不同程度的改善。结论肾上腺素β受体兴奋所诱导的心肌肥厚伴有Rho激酶信号通路的激活,Rho激酶抑制剂可改善Iso所致心肌肥厚动物模型的心功能和病理学变化。更多还原

【Abstract】 Objective To investigate the effects of Rho kinase inhibitor on myocardial hypertrophy induced by isoproterenol (Iso) in rats and its mechanisms.Methods Wistar rats were randomly divided into control, Iso model, Iso+fasudil (Fas, 2, 10 mg), and Iso+captopril (Cap) groups, 8 rats in each group. Myocardial hypertrophy models were induced by subcutaneous injection of Iso except for control group. At the end of the experiment, the following parameters were determined: the ratio of heart weight to body weight (HW/BW), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), ±dp/dtmax, myofibril diameter (MD), collagen volume fraction (CVF). RhoA and Rho kinase mRNA were tested by RT-PCR. Results Compared with those of control group, the ratio of HW/BW, LVEDP, MD, CVF, the expression levels of RhoA and Rho kinase mRNA all increased in Iso model group, but LVSP and ±dp/dtmax decreased. Fas as well as Cap improved these parameters at different levels. Conclusions Rho/Rho kinase signaling pathway may play an important role in myocardial hypertrophy induced by β-adrenergic receptor stimulation, and Rho kinase inhibitor Fas can improve the cardiac functions and pathological changes in Iso-induced myocardial hypertrophy model.更多还原