Influence Of Kaempferol On TGF-β₁/Smads Signal Transduction In Liver Tissue Of Mice With Schistosoma Japonicum Infection

Objective To investigate the effect of kaempferol on periovular granuloma and liver fibrosis in mice with schistosomiasis japonica after treatment with praziquantel.Methods Thirty two BALB/c mice were infected with cercarie of Schistosoma japonicum.Eight BALB/c mice as normal control group(GroupA) were not infected with cercarie of Schistosoma japonicum.The infected mice were divided randomly into five groups at the end of6th week after infection:praziquantel group(8mice,GroupB),low-dose group [kaempferol5mg·k g-1·d-1×4W, ltime/d,6mice,GroupC],middel-dose group [kaempferol10mg·k g-1·d-1×4W, ltime/d,6miceGroupD,],hight-dose group [kaempferol15mg·k g-1·d-1×4W, ltime/d,6mice,GroupE,], maximum-dose group [kaempferol20mg·k g-1·d-1×4W, ltime/d,6mice,GroupF].On the42nd after infection,groups B,C,D,E and F were treated with praziquantel[500mg·k g-1·d-1×2d, ltime/d].On the44nd after infection,according to the above method and dose,each of the groups C,D,E and F was treated with kaempferol for28days.Group A and B were treated with equivalent normal saline during28d. All mice were sacrificed at the end of treatment.TGF-β1,Smad2/3,Smad7,TIMP1,a-SMA, COL I, COLIII on tissue microarray sections were detected by immunohistochemistry.The lever of hepatic Smad2,Smad3,Smad7a-SMA, TIMP1, COLⅢ,mRNA was determined by qRT-PCR.Results The area of granuloma, the degree of hepatic fibrosis and the in expression of Smad2,Smad3and at protein and mRNA levels in groups C、D、E and F were significantly greater than group B(P<0.05),the expression of Smad7at protein and mRNA levels in group B was significantly lower than groups C、D、E and F(P<0.05).In groups C、D、E and F,the expression of Smad2and Smad3at protein and mRNA levels decreased progressively with increasing concentration gradient;the expression of Smad7at protein and mRNA levels was opposite. In comparison with those in the normal control group,the expression of a-SMA, TIMPl,types I and III collagen were significantly stronger in livers of praziquantel group、low-dose group、middle-dose group、hight-dose group and maximum-dose group.The levers of hepatic a-SMA, TIMP1,types Ⅰ and Ⅲ collagen in KA treated groups were lower than those in the praziquantel group.Increasing with the drug concentration of Kaempferol,the protein and mRNA expression levers of a-SMA, TIMP1,types Ⅰ and Ⅲ ollagen were significantly reduced in four dose groups.Conclusions Kaempferol can significantly reduce hepatic granuloma formation and fibrosis due to schistosome eggs, decrease the expression of TGF-β1,Smad2/3,a-SMA, TIMP1,types Ⅰ and Ⅲ collagen in mice when it is given after praziquantel administration and increase the expression of Smad7.