Salvianolic acid A attenuates vascular remodeling in pulmonary arterial hypertension rats induced by monocrotaline  

作　　者：Lian-hua FANG Yu-cai CHEN Tian-yi YUAN Yang LYU Guan-hua DU 

机构地区：[1]Beijing Key Laboratory of Drug Targets Identification and Drug Screening [2]Beijing Key Laboratoryof Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

出　　处：《中国药理学与毒理学杂志》2018年第4期279-280,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：supported by National Natural Science Foundation of China(81773935;81573645;81603101); CAMS Innovation Fund for Medical Sciences(2017-I2M-1-010)

摘　　要：OBJECTIVE Salvianolic acid A(SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge) and exhibits many pharmaco.logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats.However,whether SAA improves vascular remodeling induced by pulmonary arterial hypertension(PAH) remains unknown.In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline(MCT 60 mg·kg^(-1)).The rats were orally treated with either SAA(0.3,1,3 mg·kg^(-1)·d^(-1)) or a positive con.trol Bosentan(30 mg·kg^(-1)·d^(-1)) for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab.normalities and the subsequent increases of right ventricular systolic pressure(RVSP).Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in.jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge.netic protein type Ⅱ receptor(BMPR Ⅱ) and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa.tients at high risk of PAH.OBJECTIVE Salvianolic acid A（SAA） is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen（Salvia Miltiorrhiza Bunge） and exhibits many pharmaco.logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats.However,whether SAA improves vascular remodeling induced by pulmonary arterial hypertension（PAH） remains unknown.In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline（MCT）,and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline（MCT 60 mg·kg^（-1））.The rats were orally treated with either SAA（0.3,1,3 mg·kg^（-1）·d^（-1）） or a positive con.trol Bosentan（30 mg·kg^（-1）·d^（-1）） for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab.normalities and the subsequent increases of right ventricular systolic pressure（RVSP）.Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in.jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge.netic protein type Ⅱ receptor（BMPR Ⅱ） and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa.tients at hig

关 键 词：丹酚酸 中药 丹参 治疗方法 

分 类 号：R285.5[医药卫生—中药学] R285.5[医药卫生—中医学]