摘要：目的:探讨桂枝茯苓丸对自发性髙血压( SHR)大鼠血流状态的影响及心肌纤维化的改善作用. 方法:将28只12周龄的SHR 大鼠随机分为模型组、桂枝茯苓丸低(10 mg·(kg·d) -1)、中(20 mg·(kg·d) -1)、高(40 mg·(kg·d) -1)剂量治疗组,另设同源正常的京都大鼠(WKY)为对照组,各组大鼠数量均为7只. 桂枝茯苓丸各治疗组给予上述对应的各药物剂量灌胃给药,模型组及对照组大鼠给予20 mg·( kg·d) -1的生理盐水灌胃,连续饲养12 w后检测大鼠的血流动力学变化指标,ELISA检测试剂盒分析纤溶酶原激活物抑制物-1(PAI-1)、血管性假性血友病因子( vWF)、组织纤溶酶原激活物( t-PA)活性. 应用HE染色、Masson染色观察大鼠左心室心肌组织病理成分变化,免疫组化染色分析心肌组织中PKD1蛋白的表达变化. 结果:和模型组相比,桂枝茯苓丸各治疗组大鼠心肌血流动力学指标改善明显,左室收缩期平均压( LVSP)、左心室内压力曲线最大上升和下降速率( ± dp/dt max)、PAI-1和vWF活性均显著升高(P<0. 01);左心室舒张末期压力(LVEDP)、t-PA活性均显著降低(P<0. 01). 组织病理成分变化分析表明和模型组相比,桂枝茯苓丸各治疗组大鼠心肌组织成纤维细胞构成比例显著下降(P<0. 01),肥大细胞数量减少,细胞胞浆中PKD1蛋白的表达显著下调(P<0. 01). 结论:桂枝茯苓丸可有效改善髙血压引发的血液高凝状态,抑制SHR大鼠的心肌纤维化,改善心室重构.%Objective:To study the effect of Guizhi Fuling Wan on myocardial fibrosis of myocardium in rats with spontaneous high blood pressure and to analyze its possible mechanism. Method:28 rats with spontaneous high blood pressure(SHR)were randomly subjected to model group, 3 different dose groups of Guizhi Fuling Wan(10 20, 40 mg·(kg·d) -1), and another homologous normal Kyoto rats ( WKY) as control group, each group consisted of 7 rats. All the treatment groups were orally fed the drug, and the model group and control group were fed 0. 9% sodium chloride 20 ml·( kg·d) -1 . 12 weeks later, the rats were sacrificed, the hemody-namic changes in rats was determined, the activity of plasminogen activator inhibitor-1 (PAI-1), von pseudo hemophilia factor (vWF) and tissue plasminogen activator ( t-PA) were analyzed by ELISA assay kit. And the segmental heart samples were used for hematoxylin and eosin staining, masson staining and histological evaluation on expression of protein kinase D1(PKD1). Results: Compared with the model group, the left ventricular systolic pressure( LVSP) , maximal decrease and increase rate of pressure in left ventricle, the ac-tivity of vWF and PAI-1 in all the treatment groups and control group increased significantly(P<0. 01), while the left ventricular end diastolic pressure(LVEDP) and the activity of t-PA decreased significantly(P<0. 01). Fibroblast proportion, the number of mast cells and the expression of PKD1 protein in the cytoplasm of all the treatment groups decreased significantly, compared to the model group( P<0. 01). Conclusion:Our study reveals that Guizhi Fuling Wan can obviously alleviate the high blood coagulation state caused by hy-pertension, suppress fibrosis of myocardium in rats with spontaneous high blood pressure, and diminishing cardiac remodeling.
