| Schistosomiasis is a major parasitic disease. In schistosomiasis japonica, the major pathologic lesion is the granulomatous response to entrapped eggs and consequently hepatic fibrosis, it is the main reason that leads to the death of these patients with Schistosomiasis japonica.The strategy of anti-schistosomal hepatic fibrosis mainly include that killing worms,inhibiting periovular granulomas,delaying or even preventing from hepatic fibrosis.Even though efficacious schistosomicides are given,periovular granulomas and liver fibrosis are still developed.At present,there still have no ideal anti-hepatofibrotic drugs.Bidens bipinnata L, a species of the genus Bidens (Compositae), is widely distributed in majority province in China. Bidens bipinnata L had been traditionally used for many years. It is bitter in taste, neutral in nature and innocuity, and has the effect of heat-clearing, detoxicating and eliminating stasis to subdue swelling. It was largely used to treat hepatitis, malaria. Previous reports show it has anti-inflammatory, removal of oxygen free radicals and the regulation of the immunity. It contains many chemical compositions, such as flavonoids, eneyne, coumarins,organic acid and compound ester, triterpenoid, steroid, aetherolea. Our previous study show its effective fraction is total flavones of Bidens bipinnata L (TFB), which is extracted from the leaves of Bidens pilosa L. TFB has been verified to protect against acute liver injury induced by CCl4 and immunological liver fibrosis induced by pig serum from preclinical experimental research. To further explore the effect of total flavones of Bidens bipinnata L (TFB) on schistosomal hepatic fibrosis, the animal model was established by which cercarie of Schistosoma japonica infected mice. The mechanisms of action of TFB on liver fibrosis were studied in vivo.The main contents were divided into two sections as follows:1 Inhibitory effects and mechanisms of TFB on hepatic fibrosis in murine schistomiasisFifty Balb/C mice were infected with cercarie of Schistosoma japonica. the fortieth two days after infection, the infected mice were treated with Praziquantel (400mg/kg. d-1) for one day, then these mice were divided randomly into five groups: control group,high dose TFB group (230mg/kg. d-1),middle dose TFB group (115mg/kg. d-1),low dose TFB group (57.5mg/kg. d-1) and anti-hepatic fibrosis drugs (colchicines) group (0.15mg/kg. d-1) as positive control group. Ten healthy Balb/C mice were used in this experiment as normal control group. All animals are sacrificed at the end of the 14th weeks,Compared with control group, high dose TFB decreased mean granulomas areas and number of eggs per gram in liver tissues, TFB treatment significantly reduced ALT, AST, HA content in serum and Hyp in liver tissue. But TFB had no effect on body weight and index of liver and spleen .Pathological and morphological examination showed TFB could ameliorate appearance of liver by macroscopic observation and fibrogenesis by hematoxylin-eosin (HE) staining and masson staining. Results of immunohistochemistry showed high dose TFB treatment significantly reduced the expression levels ofα-SMA,TGF-β1,TIMP-1 and collagen type I in liver tissues. These results suggest that TFB has positively inhibitory effects on hepatic fibrosis in murine schistomiasis .which exerts its effects on hepatic fibrosis by inhibiting activation of hepatic stellate cell and synthesis of collagen.2 The therapeutic effects and mechanisms of TFB on hepatic fibrosis in mice infected schistosoma japonicaFifty Balb/C mice were infected with cercarie of Schistosoma japonica. the fortieth two days after infection, the infected mice were treated with Praziquantel (400mg/kg. d-1) for one day. The model of hepatic fibrosis was successfully established at the end of 14th week after infection,which was dependent on developmental observation. The rest thirty infected mice were divided randomly into three groups:control group,TFB group(230mg/kg.d-1)and Colchicines group (0.15mg/kg. d-1). Ten healthy Balb/C mice were viewed as normal control group. All animals are sacrificed at the end of the 20th weeks. Compared with control group, TFB treatment increased body weight of mice and decreased index of liver and spleen , TFB significantly reduced TNFαand TGF-β1 content in serum. But TFB had no effect on areas of granulomas in liver tissues . Results of pathological and morphological examination showed TFB could ameliorate appearance of liver by macroscopic observation and fibrogenesis by hematoxylin-eosin (HE) staining and masson staining. Results of immunohistochemistry showed TFB significantly reduced the expression levels of NFκB andα-SMA. And then TFB treatment could markedly down-regulated TGF-β1, procollagenα1(I), Smad3 mRNA expression and up-regulated Smad7 mRNA expression in liver by RT-PCR analysis. In addition TFB increased the number of apoptosis of activated HSC by TUNEL andα-SMA staining. These results suggest that TFB has evidently therapeutic effects on hepatic fibrosis in murine schistomiasis.Conclusion: TFB had significantly inhibitory and therapeutical effects on hepatic fibrosis in mice with schistosomiasis japonica probably by moderately regulating ova and granulomatous immune response, markedly inhibiting TGF-β1/Smads signal pathway and inducing apoptosis of activated HSC in vivo. thereby reduced number of activated HSC and content of collagen in liver tissues... |
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