Effect Of Aloeemodin And Praziquantel On Liver Fibrosis Due To Schistosoma Japonicum

Objective: The roles of aloeemodin and praziquantel in liver fibrosis induced bySchistosoma japonicum in mice was investigated. In order to investigated the curemechanism, the level of malondialdehyde (MDA),transforming growth factor beta1(TGF-β1),platelet derived growth factor(PDGF),tissue inhibitor metalloproteinase-1(TIMP-1),c-jun,c-fos,Smad2mRNA,Smad7mRNA,external-signal regulatedkinase(ERK)mRNA,cyclin dependent kinase4(CDK4)mRNA,cyclinD1mRNA,Raf-1mRNA,and collagen was detected.Methods: Eighty mice were divided into four groups: Group A, group B, group C andgroup D. Group A, group B and group C were infected withSchistosoma japonicum cercarie. After eight weeks, group A was treated with praziquantel500 mg·kg^-1·d^-1 for 2 days , group B was treated with aloeemodin 0.3 mg·kg^-1·d^-1 for 8weeks afte with praziquantel 500 mg·kg^-1·d^-1 for 2 days. Group C was taken asexperimental control without any treatment. Group D was taken as normal control. At 16thweek, all mice were sacrificed and a part of liver tissue was preserved. In every group, HEstaining was applied to observe the changes in hepatic histopathology. In every group, RT-PCR was applied to detect the expressions of hepatic Smad2mRNA,Smad7mRNA,ERKmRNA,CDK4mRNA,cyclinD1mRNA,Raf-1 mRNA. In everygroup, immunohistochemical technique was applied expression of TGF-β1,PDGF,TIMP-1,c-jun,c-fos,typeⅠand typeⅢcollagen in liver tissue.Results: Praziquantel treatment relieved the degree of hepatic fibrosis. The expressionsof hepatic Smad2mRNA,ERKmRNA,CDK4mRNA,cyclinD1mRNA,Raf-1 mRNA.TGFβ1,TIMP1, c-jun, c-fos, typeⅠand typeⅢcollagen were obviously reducedcompared to the experimental control, but them were still higher than normalcontrol. As praziquantel treatment combined with aloeemodin, the degree of hepaticfibrosis was further relieved. The expression of hepatic Smad7mRNA was obviouslyincreased compared to the experimental control. The expressions ofSmad2mRNA,ERKmRNA,CDK4mRNA,cyclinD1mRNA,Raf-1 mRNA.TGFβ1,TIMP1, c-jun, c-fos, typeⅠand typeⅢcollagen in liver tissue werereduced significantly compared to the group treated with praziquantel. The expressionsof Smad7mRNA was increased significantly compared to the group treated withpraziquantel.Conclusion: Anti-fibrotic therapy is necessary after treatment ofpraziquantel. The anti-fibrotic effect of Aloeemodin may be based onreducing the level of TGFβ1,TIMP1, PDGF, c-jun, c-fos, and inhibiting theexpressions of Smad2,ERK,CDK4,cyclinD1,Raf-1 gene, which lead toreducing the synthesis of typeⅠand typeⅢcollagen.