Abstract: Objective  To study the therapeutical effect and mechanisms of resveratrol and its combination with praziquantel on the liver fibrosis due to Schistosoma japonicum infection.  Methods  Eighty mice infected with 25 S. japonicum cercariae for 6 weeks were randomly divided into four groups named as praziquantel group （A）, resveratrol group（B）, resveratrol+praziquantel group （C） and infection group （D）. Mice in groups A and B were treated with praziquantel［500 mg/（kg·d）］ for 2 d, and resveratrol［20 mg/（kg·d）］ for 6 weeks, respectively. Mice in group C were treated with resveratrol［20 mg/（kg·d）］ for 6 weeks after praziquantel treatment［500 mg/（kg·d）×2 d］. Group D served as infection control. Twenty normal mice were taken as normal control group（Group E）. At the 12th week post-infection, all mice were sacrificed and the liver tissues were removed. Histopathological changes were observed in the liver of all groups. RT-PCR was used to detect the relative VEGF mRNA level in liver tissue. Maleic dialdehyde （MDA） content and superoxide dismutase（SOD） activity in liver were measured by ELISA. The expressions of VEGF, typeⅠ and type Ⅲ collagen were examined by immunohistochemistry.  Results  After treatment, the degrees of liver fibrosis in groups A, B and C decreased. The hepatic expression of VEGF mRNA and VEGF protein levels in groups A（0.37±0.06, 0.69±0.42）, B （0.23±0.01, 0.38±0.42）, C（0.11±0.00, 0.12±0.17） and E（0.06±0.03， 0.04±0.02） were lower than that of group D （0.60±0.03， 0.97±0.36）（P<0.01）, those in groups A and B were significantly lower than that of group C（P<0.01 or P<0.05）, and those in group A were lower than in group B（P<0.05）. There was no significant difference in liver SOD activity and MDA content between group A（13.56±2.56, 7.62±2.30） and group B（14.28±1.56, 6.63±2.31）（P>0.05）. Compared with group C（22.36±1.55, 2.31±1.31）, mice in groups A and B exhibited decreased an SOD activity, but increased MDA content （P<0.05）. SOD activity of groups A, B, and C was higher than that of group D （P<0.05 or P<0.01）, and MDA content in the above three groups was lower than that of group D（P<0.05 or P<0.01）.  Conclusion  Resveratrol has an antifibrogenic effect through inhibiting the expression of VEGF and reducing oxidative stress in mice with Schistosoma japonicum egg-induced liver fibrosis. Resveratrol and praziquantel show a synergistic action in antifibrosis treatment.

Key words: Schistosoma japonicum, Liver fibrosis, Resveratrol, VEGF, Oxidative stress