Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model  

作　　者：Yu-cai CHEN Tian-yi YUAN Hui-fang ZHANG Dan-shu WANG Yu YAN Zi-ran NIU Yi-huang LIN Lian-hua FANG Guan-hua DU 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines [2]Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

出　　处：《Acta Pharmacologica Sinica》2016年第6期772-782,共11页中国药理学报（英文版）

摘　　要：Aim： The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension （PAH）. In this study we examined whether salvianolic acid A （SAA） extracted from the traditional Chinese medicine ＇Dan Shen＇ attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods： PAH was induced in rats by injecting a single dose of monocrotaline （MCT 60 mg/kg, sc）. The rats were orally treated with either SAA （0.3, 1, 3 mg.kg-l.d-1） or a positive control bosentan （30 mg.kgl.d-1） for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and thickness were calculated, and biochemical and histochemica in the lungs were measured using immunoblotting. ungs were harvested, the organ indices and pulmonary artery wall analysis were conducted. The levels of apoptotic and signaling proteins Results： Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure （RVSP）. Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury 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 morphogenetic protein type II receptor （BMPRII） and phosphorylated Smadl/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 patients at high risk of PAH.Aim： The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension （PAH）. In this study we examined whether salvianolic acid A （SAA） extracted from the traditional Chinese medicine ＇Dan Shen＇ attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods： PAH was induced in rats by injecting a single dose of monocrotaline （MCT 60 mg/kg, sc）. The rats were orally treated with either SAA （0.3, 1, 3 mg.kg-l.d-1） or a positive control bosentan （30 mg.kgl.d-1） for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and thickness were calculated, and biochemical and histochemica in the lungs were measured using immunoblotting. ungs were harvested, the organ indices and pulmonary artery wall analysis were conducted. The levels of apoptotic and signaling proteins Results： Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure （RVSP）. Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury 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 morphogenetic protein type II receptor （BMPRII） and phosphorylated Smadl/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 patients at high risk of PAH.

关 键 词：salvianolic acid A Dan Shen BOSENTAN MONOCROTALINE pulmonary artery hypertension vascular remolding APOPTOSIS BMPRII SMAD 

分 类 号：S858.31[农业科学—临床兽医学] S858.966[农业科学—兽医学]