Cardioprotection and matrix metalloproteinase-9 regulation of salvianolic acids on myocardial infarction in rats.
Acute myocardial infarction (AMI) remains the leading cause of mortality in the world. Early intervention using salvianolic acids (SA) can substantially improve clinical outcomes. However, in spite of the great achievements that have been made in elucidating the protective effects of SA on AMI, the effects of SA on the contractile performance of the left ventricle (LV) and the underlying mechanism are still not so clear. In the present study, AMI was introduced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Administration of SA significantly decreased infarct size, improved LV function and appearance of the myocardium and decreased myocardial malondialdehyde levels compared with the AMI group. Furthermore, treatment with SA significantly downregulated the mRNA expression level and activity of matrix metalloproteinase-9 (MMP-9), but did not regulate the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression level at the infarct area. Lisinopril (an angiotensin converting enzyme inhibitor), which holds potential effects on cardioprotection, was chosen as the positive control in this study. Lisinopril elevated LV function and appearance of the myocardium, decreased malondialdehyde levels without an influence on infarct size, and regulated the MMP-9 enzyme level but not the MMP-9 mRNA and TIMP-1 protein levels. These findings suggest that early SA treatment is effective to improve LV function; and SA may exert preventative effects against myocardial remodeling after infarction.
Jiang
Baohong
B
Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.
Wu
Wanying
W
Li
Ming
M
Xu
Lingling
L
Sun
Kejia
K
Yang
Min
M
Guan
Shuhong
S
Liu
Xuan
X
Guo
De-an
DA
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D007773:Lactates / Q000494:pharmacology*; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects; D053630:Depsides
D001572:Benzofurans; D002109:Caffeic Acids; D002316:Cardiotonic Agents; D007773:Lactates; D017706:Lisinopril; D008315:Malondialdehyde; D020780:Matrix Metalloproteinase 9; D010936:Plant Extracts; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C066201:salvianolic acid A; C076944:salvianolic acid B; D053630:Depsides