Study on Mechanism of Improvement Effects of Astragaloside IV on Hepatic Fibrosis Model Rats

OBJECTIVE To observe the improvement effect of astragaloside IV on CCl4-induced hepatic fibrosis model rats and its possible mechanism.METHODS SD rats were randomly divided into normal group, model group, silibinin group(30 mg·kg^-1), and astragaloside IV group(14 mg·kg^-1). The hepatic fibrosis model was established by intraperitoneal injection of 50% CCl4 olive oil solution(1.5 mL·kg-1) twice a week for 8 weeks. Then rats in each group were given the corresponding drugs by intragastric administration of 10 mL·kg^-1 per day for 4 weeks. Detected the content of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in rat serum. Calculated the liver index. Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes of liver tissue. Western blotting were used to detect the protein expression level of transforming growth factor(TGF-β1), epithelial-mesenchymal transition(EMT) markers E-cadherin,N-cadherin and α-smooth actin(α-SMA). Real-time PCR were used to detected the mRNA expression levels of TGF-β1 and E-cadherin.RESULTS Compared with the normal group, the liver index of rats in the model group was significantly increased(P<0.01), the contents of ALT and AST in the serum were significantly increased(P<0.01), the collagen volume fraction was significantly increased(P<0.01), and TGF-β1 mRNA in the liver tissue and protein expression levels increased(P<0.05 or P<0.01), E-cadherin protein expression was significantly decreased(P<0.01), α-SMA, N-cadherin protein expression was significantly increased(P<0.01). Compared with the model group, the liver index in the astragaloside IV group significantly decreased(P<0.01), the serum ALT and AST content was significantly decreased(P<0.01), the collagen volume fraction was significantly decreased(P<0.01), and E-cadherin in the liver tissue protein expression was up-regulated(P<0.05), α-SMA,N-cadherin protein expression was significantly down-regulated(P<0.01), TGF-β1 protein and mRNA expression decreased(P<0.01 or P<0.05).CONCLUSION Astragaloside IV has an ameliorating effect on CCl4-induced hepatic fibrosis model rats, and its mechanism may be related to down-regulation of N-cadherin, α-SMA, TGF-β1 protein expression and up-regulation of E-cadherin protein expression.