Effect Of Quercetin And Praziquantel On Liver Fibrosis And Myocardial Injury Due To Schistosoma Japonicum Infection

Objective: To study the effects and mechanisms of myocardial injury in schistosome-infected mice. To investigate the effects and mechanisms of quercetin on the development of hepatic fibrosis and myocardial injury after being treated with praziquantel.Methods: Eighty mice were divided into four groups: Group A, group B, group C and group D. Group A, group B and group C were infected with Schistosoma japonicum cercarie. After eight weeks, group A was treated with praziquantel 500 mg·kg-1·d-1for 2 days , group B was treated with quercetin 30 mg·kg-1·d-1 for 8 weeks after being treated with praziquantel 500 mg·kg-1·d-1 for 2 days. Group C was taken as experimental control without any treatment. Group D was taken as normal control. At 16th week, all mice were sacrificed and a part of liver tissue and myocardium tissue were preserved. In every group, HE staining and electric microscope were applied to observe the changes in hepatic histopathology and cardiac histopathology and myocardial ultramicrostructure . In every group, RT-PCR was applied to detect the expressions of hepatic c-fos mRNA and c-jun mRNA. In every group, immunohistochemical technique was applied to detect the expression of VEGF in liver tissue as well as the expressions of TGFβ1, TIMP1, typeⅠand typeⅢcollagen in liver tissue and myocardium tissue.Results: Praziquantel treatment relieved the degree of hepatic fibrosis. The expressions of hepatic c-fos mRNA, c-jun mRNA , VEGF, TGFβ1,TIMP1, typeⅠand typeⅢcollagen were obviously reduced compared to the experimental control, but them were still higher than normal control. As praziquantel treatment combined with quercetin, the degree of hepatic fibrosis was further relieved. The expressions of c-fos mRNA, c-jun mRNA, TGFβ1, TIMP1,typeⅠand typeⅢcollagen in liver tissue were reduced significantly compared to the group treated with praziquantel. There was different degree of myocardial injure among three groups of experimental control, praziquantel treatment, quercetin combined with praziquantel treatment. Praziquantel treatment reduced the degree of myocardial injure. The expressions of myocardial TGFβ1,TIMP1, typeⅠand typeⅢcollagen were reduced compared to the experimental control, but them were still higher than normal control. As praziquantel treatment combined with quercetin, the degree of myocardial injure was further relieved. The expressions of TGFβ1,typeⅠand typeⅢcollagen in myocardium tissue were obviously reduced significantly compared to the group treated with praziquantel, but there was no difference in the content of TIMP1 between two groups.Conclusion: Anti-fibrotic therapy is necessary after treatment of praziquantel. The anti-fibrotic effect of quercetin may be based on reducing the level of VEGF and inhibiting the expressions of c-fos gene and c-jun gene, which lead to reducing the synthesis of TGFβand TIMP1. Hepatic cirrhosis due to advanced schistosomiasis may lead to cardiac remodeling by stimulating the synthesis of TGFβand TIMP1 in myocardium. Anti-fibrotic therapy can reduce the degree of cardiac remodeling. Quercetin may protect myocardium through decreasing the level of myocardial TGFβ1.