| Background and Objective:Schistosomiasis is a kind of severe parasitosis in the developing country of tropical zone and subtropical zone. According to the World Health Organization reported that, this disease is epidemic in 74 countries of the global, more than 600,000,000 populations are threatened, and more than 200,000,000 populations were infected. After efficacious schistosomicides were given, hepatic fibrosis still continued to progress. Schistosomiasis japonica incidence had decreased from 1950s to 1980s in China, but it has risen in recent years. Liver fibrosis was the main reason that hazarded to the patients with advanced Schistosomiasis japonica. To investigate the expression of collagen type I, collagen type III,α-SMA, transforming growth factor-β1, TβRI, Smad2/3, Smad4 and Smad7 in Schistosoma japonicum-fibrotic liver tissues and to explore the Schistosoma japonicum-fibrogenic molecular mechanism, we have done a series of experiments.Methods:Eighty healthy ICR mice were randomly divided into model group and control group. The mice of model group were infected with cercaria of Schistosoma japonica. Each group of mice was given the conventional diet. The mice of both groups were killed at the end of the 4th, 6th, 8th and 12th wk respectively, and their livers, spleens, and bodies were weighed. Liver tissues were taken for HE and scarlet staining. Tissue microarrays were prepared and immunohistochemical staining was used to detect the expression of collagen type I, collagen type III,α-SMA, transforming growth factor-β1, TβRI, Smad2/3, Smad4 and Smad7. Results:Comparison with those in control group, the livers and spleens of model mice were heavier and the ratio of liver/body was higher (liver, 12 wk: 2.99±0.28 g vs 1.83±0.13g; spleen, 12 wk: 0.87±0.15 g vs 0.14±0.02 g; the ratio of liver/body, 12 wk: 9.00±1.00 vs 4.00±0.00; all P < 0.01); the expression of TGF-β1, Smad2/3, TβRI, collagen type I,α-SMA was significantly stronger in the livers of model mice (TGF-β1, 12 wk: 0.105±0.008 vs0.024±0.002; Smad2/3, 12 wk: 0.094±0.009 vs0.003±0.001; TβRI, 12wk: 0.079±0.023vs0.017±0.010; collagen type I, 12wk: 0.196±0.035vs0.050±0.017;α-SMA, 12wk: 0.096±0.020vs0.009±0.004, all P<0.01), and the above indexes were positively correlated with the degrees of hepatic fibrosis (r = 0.635, 0.482, 0.646, 0.347, 0.662, 0.475, 0.650, 0.403, respectively; all P < 0.05). Smad4 was found increased in the livers of model mice, but its expression decreased with the development of hepatic fibrosis (4 wk: 0.075±0.011 vs 0.023±0.006, 6 wk: 0.043±0.008 vs 0.010±0.002, 8 wk:0.038±0.009 vs 0.003±0.002, 12 wk: 0.028±0.004vs 0.013±0.006, all P < 0.01). Smad7 expression heightened only at the 8th wk. The expression of collagen type III was stronger from the 6th wk to 12th wk compared with those in control group, and it arrived at peak value at the 6wk , after that it began to decrease at the 8th wk.Conclusion:1. We successed in making liver fibrosis model of Schistosoma japonicum in this study.2. TGF-β1/Smads signaling pathway played an important role in liver fibrogenesis of Schistosoma japonicumm; expression of TGF-β1, Smad2/3 and TβRI were significantly increased in model mice, they might take main effect on TGF-β1/Smads signaling pathway.3. Smad4's effects might occur at early and middle stage of hepatic fibrosis.4. Expression of Smad7 transiently rose only at the 8th wk, this feedback inhibitor of TGF-βsignaling might be transcriptionally activated by TGF-β1/Smads signaling.5. Expression of collagen type I and III was strengthened in the tissue of hepatic fibrosis induced by Schistosomiasis japonica, and expression of collagen type I was predominant, but expression of collagen type III mainly increased at early stage of hepatic fibrosis and decreased at middle and advanced stage.6.α-SMA was expressed by myofibroblast, its dexpression was considerable stronger during the 6th wk to12th wk, which indicated greatly proliferation of MFBs, and then massive collagen was produced by them. Proliferation and activation of MFBs was regulated by TGF-β1/Smads signaling pathway.
|
PDF Full Text Request