Treatment with cardiotonic pills(®)  after ischemia-reperfusion ameliorates myocardial fibrosis in rats.
OBJECTIVE
The present study was designed to evaluate whether CP was beneficial in alleviating myocardial fibrosis following I/R injury.


METHODS
Sprague-Dawley rats were subjected to 30 minutes occlusion of the LADCA, followed by reperfusion. CP (0.4 or 0.8 g/kg) was daily administered starting from three hour after reperfusion until day 6. Coronary venular diameter, RBC velocity, albumin leakage, MBF, heart function, myocardial infarction and fibrosis size, myocardium ultrastructure, MPO activity, and MDA level were evaluated. The expression of MCP-1, RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, and the infiltration of leukocytes were examined.


RESULTS
CP post-treatment ameliorated I/R-induced myocardial RBC velocity reduction, MBF decrease, cardiac dysfunction, and albumin leakage increase. Moreover, myocardial infarction and fibrosis size, MPO activity, MDA level, the expression of RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, the number of CD68-positive cells increased significantly after I/R, and myocardium collagen deposition was observed on day 6 after reperfusion. All the alterations after I/R were significantly ameliorated by CP.


CONCLUSIONS
Post-treatment with CP ameliorates I/R-induced myocardial fibrosis, suggesting that CP may be applied as an option for preventing cardiac remodeling after I/R injury.
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Xiao-Hong
XH
Wei
Yu-Ying
YY
Liu
Quan
Q
Li
Li
L
Yan
Bai-He
BH
Hu
Chun-Shui
CS
Pan
Zhi-Xin
ZX
Li
Xin
X
Chang
Jing-Yu
JY
Fan
Na
N
Zhao
Kai
K
Sun
Ping
P
Huang
Chuan-She
CS
Wang
Tai-Ping
TP
Fan
Jing-Yan
JY
Han
D000199:Actins / Q000378:metabolism; D000818:Animals; D001892:Camphanes / Q000008:administration & dosage; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000473:pathology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053723:Panax notoginseng; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
D000199:Actins; D001892:Camphanes; D002316:Cardiotonic Agents; D018932:Chemokine CCL2; D004365:Drugs, Chinese Herbal; D008315:Malondialdehyde; D020780:Matrix Metalloproteinase 9; D009195:Peroxidase; D053773:Transforming Growth Factor beta1; C491766:Ccl2 protein, rat; C498862:Acta2 protein, rat; C572337:Mmp9 protein, rat; C022871:isoborneol