AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibr...AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-ga展开更多
AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with li...AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine(DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin(IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells(KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were cocultured with KCs in vitro to assess the effects of UCMSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UCMSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the coculture system resulted in decreased KC mobilization.CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.展开更多
文摘AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-ga
基金Supported by National Natural Science Foundation of China,No.81072913
文摘AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine(DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin(IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells(KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were cocultured with KCs in vitro to assess the effects of UCMSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UCMSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the coculture system resulted in decreased KC mobilization.CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.
