Abstract 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.［Chin J Contemp Pediatr, 2009, 11 (4):291-295］
WANG Zhou-Ping,HUA Yi-Min,ZHANG Xin et al. Effect of resveratrol on myocardial fibrosis in mice with chronic viral myocarditis[J]. 中国当代儿科杂志, 2009, 11(04): 291-295.
WANG Zhou-Ping,HUA Yi-Min,ZHANG Xin et al. Effect of resveratrol on myocardial fibrosis in mice with chronic viral myocarditis[J]. CJCP, 2009, 11(04): 291-295.
［6］Olson ER, Nauqle JE, Zhang X, Bomser JA, Meszaros JG. Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol［J］. Am J Physiol Heart Circ Pyhsiol, 2005, 288(3):1131-1138.
［7］Yoshida Y, Shioi T, Izami T. Resveratrol ameliorates experimental autoimmune myocarditis［J］. Circ J, 2007, 71(3):397-404.
［9］Doering CW, Jalil JE, Janicki JS, Pick R, Aghili S, Abrahams C, et al. Collagen network remodelling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophy［J］. Cardiovasc Res, 1988, 22(10): 686-695.
［10］Yu R, Hebbar V, Kim DW, Mandlekar S, Pezzuto JM, Kong AN. Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with mitogen-activated protein kinase pathways［J］. Mol Pharmacol, 2001, 60(1):217-224.
［11］EI-Mowafy AM, White RE. Resveratrol inhibits MAPK activity and nuclear translcation in coronary artery smooth muscle: reversal of endothelin1 stimulatory effects［J］. FEBS Let, 1999, 451(1):63-67.
［12］Haider UG, Sorescu D, Griendling KK, Vollmar AM，Dirsch VM. Resveratrol suppresses angittensin II-induced Akt/Protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells［J］. Mol Pharmacol, 2002, 62(4):772-777.
［15］Querejeta R, Varo N, Lopez B, Larman M, Artinano E , Iuan C, et al .Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease［J］. Circulation, 2000, 101(14):1729-1735.
［16］Querejeta R, Lopez B, Gonzalez A, Sanchez E, Larman M, Martinez Ubago JL, et al. Increased collagen type I synthesis in patients with heart failure of hypertensive origin:relation to myocardial fibrosis［J］.Circulation, 2004, 110(10): 1263-1268.
［17］Nojgaard C, Johansen JS, Christensen E, Skovgaard LT, Price PA, Becker U, et al. Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease［J］. J Hepatol, 2003, 39(2):179-186.
