Effect of kaempferol on the expression of hepatic α-smooth muscle actin, tissue inhibitor of metalloproteinase 1 and collagen in liver fibrosis of mice infected with schistosomiasis japonicum

Abstract

Objective To investigate the effect of kaempferol on periovular granuloma and liver fibrosis in mice with schistosomiasis japonicum after treatment with praziquantel.Methods BALB/c mice infected with schistosomiasis japonicum were used for animal model of liver fibrosis.Forty BALB/c mice were randomly divided into a normal group (8 mice),a model group (8 mice),and 4 kaempferol groups with different kaempferol dosages [5,10,15,20 mg/(kg·d) respectively,6 mice each group].Besides the normal group,all the mice in the other 5 groups were infected with Schistosoma japonicum,and 6 weeks after the infection,were treated with praziquantel 500 mg/(kg·d) for 2 d.Kaempferol groups were administered intragastrically with kaempferol 5,10,15,20 mg/(kg·d) respectively for 6 weeks.The mice in normal group and model group were administered with normal saline for 6 weeks.All mice were sacrificed at the end of treatment.The protein expression of tissue inhibitors of metalloproteinases(TIMP)1,α-smooth muscle actin(α-SMA),type Ⅰ collagen (COL Ⅰ),type Ⅲ collagen (COLⅢ) on tissue microarray sections was detected by immunohistochemistry.The levels of mRNA expression of hepatic α-SMA,TIMP1,CO Ⅲ,mRNA were determined by RT-PCR.Results The relative mRNA expression levels of α-SMA,TIMP1,COL Ⅲ in liver tissues of kaempferol 20 mg/(kg·d) group were 1.251 7±0.053 8,1.490 1±0.042 9 and 1.328 3±0.070 3.The relative mRNA expression levels of α-SMA,TIMP1,COLⅢ in liver tissues of modle group were 2.141 7±0.038 6,4.281 7±0.089 1 and 5.218 3± 0.121 6.The levels of mRNA expression of hepatic α-SMA,TIMP1,type Ⅲ collagen in kaempferol treated groups were lower than those in the modle group.There was significant difference among the five groups (F=36.93,95.16,48.29,P＜0.05).Increasing with the drug concentration of kaempferol,the mRNA expression levels of α-SMA,TIMP1,type Ⅲ collagen were significantly reduced in four dose groups,there was significant difference among the four groups (F=70.62,290.51,407.25,P＜0.05),and the protein expression levels of α-SMA,TIMP1,types Ⅰ and Ⅲ collagen were significantly reduced in four dose groups,there was significant difference among the four groups (F=210.92,77.41,186.33,53.18,P＜0.05).Conclusion By inhibiting the expressions of α-SMA,TIMP1,ypes Ⅰ and Ⅲ collagen,kaempferol can significantly reduce the degree of hepatic fibrosis caused by schistosome eggs. Key words: Schistosomiasis; Kaempferol; Hepatic fibrosis; α-smooth muscle actin; Tissue inhibitor of metalloproteinase; Type Ⅰ collagen; Type Ⅲ collagen