[Effect of resveratrol on myocardial fibrosis in mice with chronic viral myocarditis].
OBJECTIVE
Some research has shown that resveratrol can ameliorate myocardial injury and improve cardiac function in mice with acute viral myocarditis (VMC), and can inhibit cardiac fibroblast proliferation and myofibroblast differentiation in vitro. This study was designed to investigate whether resveratrol has similar effects in the mouse model of chronic VMC.


METHODS
One hundred mice were inoculated with 0.3 mL of Coxsackievirus B3 1*106 TCID50. Thirty days later, the survivors (n=62) were used as a model of chronic VMC, and were randomly assigned to 4 groups: untreated VMC, and low- (10 mg/kg), middle- (100 mg/kg) and high-dose (1 000 mg/kg) resveratrol-treated VMC (once daily, for 30 days). Ten mice which received neither Coxsackievirus B3 nor resveratrol treatment served as the control group. After 30 days of resveratrol treatment, the mice were sacrificed. Serum concentrations of collagenous pre-peptides (PINP, PICP and PIIINP) were assessed using ELISA. Hematoxylin-eosin staining, picrosirius red staining and circularly polarized light were used to examine the histochemistry of myocardial collagen.


RESULTS
The myocardial collagen volume fraction in the high-dose (0.74+/-0.19) and the middle-dose (1.07+/-0.12) resveratrol-treated VMC groups was significantly lower than that in the untreated VMC (2.33+/-0.18) and the low-dose resveratrol-treated VMC (2.17+/-0.19) groups (P<0.05). Compared with the untreated VMC group, serum concentrations of PICP and PIIINP in the high-dose and the middle-dose resveratrol-treated VMC groups were significantly reduced (P<0.05), while PINP concentrations increased significantly (P<0.05).


CONCLUSIONS
Resveratrol can inhibit hyperplasia of myocardial collagen in the mouse model of chronic VMC, acting as an effective anti-fibrotic agent in the myocardium.
Wang
Zhou-Ping
ZP
Department of Children's Cardiovascular Disease, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Hua
Yi-Min
YM
Zhang
Xing
X
Wang
Yi-Bin
YB
Shi
Xiao-Qing
XQ
Li
Ming-Yuan
MY
D000818:Animals; D002908:Chronic Disease; D024042:Collagen Type I / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D003384:Coxsackievirus Infections / Q000188:drug therapy*; D029822:Enterovirus B, Human; D005355:Fibrosis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*
D024042:Collagen Type I; D024043:Collagen Type II; D010446:Peptide Fragments; D011347:Procollagen; D013267:Stilbenes; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D000077185:Resveratrol