Abstract:Objective:To investigate the effects of vasonatrin peptide (VNP), a synthetic novel natriuretic peptide, on liver fibrosis.
Methods:Male Balb/c mice were randomized into corn oil control group (control group for short, protocol: corn oil 1 mL/kg ip. twice a week for 12 weeks), liver fibrosis group (model group for short, protocol: CCl4 1 mL/kg ip. twice a week for 12 weeks, and saline 1 mL/kg iv. once daily for the last 6 weeks) and hepatic fibrosis+VNP treatment group (VNP treatment group for short, protocol: CCl4 1 mL/kg twice a week for 12 weeks, and VNP 50 μg/kg iv. once daily for the last 6 weeks). The liver samples were harvested from mice on the 3rd day of the last injection to evaluate the histopathological change and fibrotic level of the liver. The mouse hepatic stellate cell line (HSC-T6) was cultured in vitro and was exposed to VNP of different concentrations, and then the DNA and collagen synthesis of the cells were determined by [3H]-thymidine and [3H]-proline incorporation assay, respectively.
Results:The livers of the model group presented significant impairment and collagen accumulation compared with that of the control group. However, the hepatic impairment and collagen accumulation induced by CCl4 was effectively alleviated by treatment with VNP. Liver collagen concentration of control group, model group and VNP treatment group was (43.6±6.3) μg/mg, (93.5±7.2) μg/mg and (62.2±5.1) μg/mg, respectively, and the differences were statistically significant (P<0.05). The [3H]-thymidine and [3H]-proline incorporation rate of HSC-T6 after exposure to VNP (10-7 mol/L) was decreased by 48.5% and 43.7%, respectively (both P<0.05).
Conclusions:VNP has inhibitory effect on CCl4-induced liver fibrosis, which may probably be associated with its effect of inhibiting the proliferation and collagen production of hepatic stellate cells.