Cardioprotective effect of salvianolic acid B on large myocardial infarction mediated by reversing upregulation of leptin, endothelin pathways, and abnormal expression of SERCA2a, phospholamban in rats.
OBJECTIVE
To study the cardioprotective effect of salvianolic acid B (Sal B) on cardiac dysfunction. We hypothesized that hyperleptinemia may correlate with abnormal expression of sarco/endoplasmic reticulum ATPase 2a (SERCA2a), phospholamban (PLB) and endothelin-reactive oxygen species (ET-ROS) pathways in rats with large myocardial infarction (MI).


METHODS
Large MI was produced by coronary artery ligation for 4 weeks in rats. The rats were divided into four groups: sham, MI, MI+l-Sal B (50 mg/(kg d)), p.o. for 4 weeks), and MI+h-Sal B (100 mg/(kg d)), p.o. for 4 weeks).


RESULTS
In MI rats, hemodynamic and echocardiographic abnormalities, cardiac remodeling, and histological changes with features of cardiac failure were associated with hyperleptinemia accompanied by oxidative stress and upregulated OB-Rb, ET pathway mRNA expression and downregulated SERCA2a and PLB mRNA and protein expressions in the myocardium.


CONCLUSIONS
The studies demonstrated that an activated leptin pathway correlated with abnormal expression of SERCA2a, PLB and an activated ET-ROS system in the affected myocardium. Sal B exerts beneficial actions on cardiac function in rats with large MI, mainly suppressing upregulation of leptin and ET pathways and oxidative stress, and recovering the normal expressions of SERCA2a and PLB in myocardium.
He
Haibo
H
Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zijingang Campus, Zhejiang University, Hangzhou, China.
Shi
Mengqiong
M
Zeng
Xiaowei
X
Yang
Jun
J
Li
Yikui
Y
Wu
Limao
L
Li
Lianda
L
D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020738:Leptin / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism; D000099211:Phospholamban; D053630:Depsides
D001572:Benzofurans; D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D016232:Endothelins; D020738:Leptin; D017382:Reactive Oxygen Species; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C506948:Atp2a2 protein, rat; C076944:salvianolic acid B; D053630:Depsides