Yuanmin Li1, Linlin Wang2, Zhihui Dong3, Shiying Wang4, Lili Qi5, Kenka Cho6, Zhou Zhang2, Na Li2, Yurong Hu7, Baohong Jiang8. 1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China. 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. 3. Departments of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 4. Agricultural University of Hebei Province, Baoding 071001, Hebei, China. 5. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Agricultural University of Hebei Province, Baoding 071001, Hebei, China. 6. Takarazuka University of Medical and Health Care, Hanayashiki-Midorigaoka, Takarazuka City 6660162, Japan. 7. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: huyr@zzu.edu.cn. 8. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jiangbh@simm.ac.cn.
Abstract
BACKGROUND: Following myocardial infarction (MI), a series of structural and functional changes evolves in the myocardium, collectively defined as cardiac remodeling. PURPOSE: The aim of present study was to investigate the cardioprotection of salvianolicacid B (SalB) and ginsenoside Rg1 (Rg1) combination against cardiac remodeling in a rat model at the subacute phase of MI and further elucidate the underlying mechanism. METHODS: Rat heart was exposed via a left thoracotomy at the fourth intercostal space and MI was induced by a ligature below the left descending coronary artery. Hemodynamic assay was conducted using a Mikro-tipped SPR-320 catheter which was inserted through the right carotid artery into left ventricle.Myocardial infarct size was detected using 3,5-triphenyltetrazolium chloride (TTC) staining. Haematoxylin and eosin (HE) stain and picric sirius red stain were conducted for histopathological detection. Immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-SMA) and gelatin zymography was used to evaluate the activities of matrix metalloproteinase-9 (MMP-9). RESULTS: Comparing with MI rats, 30 mg/kg SalB-Rg1 improved cardiac function verified by maximum rate of pressure development for contraction (+dp/dtmax, p < 0.01) and maximum rate of pressure development for relaxation (-dp/dtmax, p < 0.05); reduced myocardial infarct size (p < 0.05) verified by TTC staining, improved cardiac structure based on HE stain; decreased collagen volume fraction (p < 0.05) and collagen I/III ratio (p < 0.05) according picrosirius red staining. The underlying mechanism of SalB-Rg1 against cardiac remodeling was associated with its down-regulation on α-SMA expression according immunohistochemistry (p < 0.01) and inhibition on MMP-9 activity based on in-gel zymography (p < 0.05). CONCLUSION: All above study indicated the potential therapeutic effects of SalB-Rg1 on heart.
BACKGROUND: Following myocardial infarction (MI), a series of structural and functional changes evolves in the myocardium, collectively defined as cardiac remodeling. PURPOSE: The aim of present study was to investigate the cardioprotection of salvianolicacid B (SalB) and ginsenoside Rg1 (Rg1) combination against cardiac remodeling in a rat model at the subacute phase of MI and further elucidate the underlying mechanism. METHODS:Rat heart was exposed via a left thoracotomy at the fourth intercostal space and MI was induced by a ligature below the left descending coronary artery. Hemodynamic assay was conducted using a Mikro-tipped SPR-320 catheter which was inserted through the right carotid artery into left ventricle.Myocardial infarct size was detected using 3,5-triphenyltetrazolium chloride (TTC) staining. Haematoxylin and eosin (HE) stain and picric sirius red stain were conducted for histopathological detection. Immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-SMA) and gelatin zymography was used to evaluate the activities of matrix metalloproteinase-9 (MMP-9). RESULTS: Comparing with MI rats, 30 mg/kg SalB-Rg1 improved cardiac function verified by maximum rate of pressure development for contraction (+dp/dtmax, p < 0.01) and maximum rate of pressure development for relaxation (-dp/dtmax, p < 0.05); reduced myocardial infarct size (p < 0.05) verified by TTC staining, improved cardiac structure based on HE stain; decreased collagen volume fraction (p < 0.05) and collagen I/III ratio (p < 0.05) according picrosirius red staining. The underlying mechanism of SalB-Rg1 against cardiac remodeling was associated with its down-regulation on α-SMA expression according immunohistochemistry (p < 0.01) and inhibition on MMP-9 activity based on in-gel zymography (p < 0.05). CONCLUSION: All above study indicated the potential therapeutic effects of SalB-Rg1 on heart.