中文摘要：

目的：观察法舒地尔对压力超负荷大鼠心肌肝细胞生长因子（HGF）表达的影响,探讨法舒地尔防治心肌纤维化的作用机制。方法：采用腹主动脉缩窄法建立压力超负荷心肌纤维化大鼠模型。假手术组（n=8）仅分离但不予结扎腹主动脉。术后4周末,将手术组存活的28只大鼠随机分为模型组（n=10）、法舒地尔高剂量组（FH组,n=9）和法舒地尔低剂量组（FL组,n=9）。药物干预4周后,计算大鼠心脏质量指数（HMI）和左心室质量指数（LVMI）。观察心肌病理学改变,测量胶原容积分数（CVF）和血管周围胶原容积分数（PCVF）。免疫组织化学法分析心肌α-平滑肌肌动蛋白（α-SMA）、磷酸化肌球蛋白磷酸酶靶蛋白亚基1（p-MYPT1）、HGF和转化生长因子-β1（TGF-β1）的表达。结果：FH和FL组较模型组HMI、LVMI、CVF、PCVF及α-SMA、p-MYPT1、TGF-β1的平均光密度值明显降低,HGF的平均光密度值明显升高（P均〈0.05）,且FH组与FL组相比作用更明显。结论：法舒地尔改善压力超负荷大鼠心肌纤维化的作用可能与促进HGF的表达有关。

英文摘要：

Objective： To observe the effect of Fasudil on expression level of myocardial hepatocyte growth factor （HGF） in pressure-overload rats and investigate the mechanisms involved in anti- myocardial fibrosis effect of Fasudil. Methods： Pressure overload induced myocardial fibrosis models were established by abdominal aortic constriction. In Sham group （n = 8） , the abdominal aorta of rat was just separated but not ligated. After operation for 4 weeks, 28 survival rats in operation group were randomly divided into 3 groups, which were Model group （n = 10）, Fasudil-High dose group （FH group, n = 9） and Fasudil-Low dose group （FL group, n = 9）. Another 4 weeks after drug intervention, the heart mass indexes （HMI） and left ventrieular mass indexes （LVMI） of rats were calculated. Pathological changes of the myocardium were observed to assess the collagen volume fraction （CVF） and perivascular collagen volume fraction （PCVF）. The expression levels of a-smooth muscle actin （α-SMA）, phosphorylated myosin phosphatase target subunit 1 （p-MYPT1）, HGF and transforming growth faetor-β1 （TGF-β1） were analysed by immunohistochemistry. Results： The HMI, LVMI, CVF, PCVF and mean optical density of α-SMA, p-MYPT1 and TGF-β1 in FH and FL groups were significantly decreased compared with those of Model group （P〈0. 05）, whereas the mean optical density of HGF was markedly increased （all P〈0. 05）. The effects in FH group were more obvious than those in FL group. Conclusion： Fasudil may attenuate pressure-overload rats＇ myocardial fibrosis by enhancing the expression of hepatocyte growth factor.