Abstract:

AIM:To analyze the effects of ginsenoside-induced bone marrow mesenchymal stem cells (BMSC) on liver regeneration and Wnt/β-catenin signaling in rats with acute liver failure (ALF).  METHODS:Sixty-six Wistar male rats of SPF grade were selected. One of them was cultured with BMSCs. Fifty rats were randomly selected to prepare ALF model.After 24 hours,5 of them were randomly selected and sacrificed.The success of the rat model was judged by liver function and histopathology.The remaining 15 rats were intraperitoneally injected with an equal dose of 0.9% sodium chloride solution as a normal group.Forty-five rats were randomly divided into three groups:BMSCs group,model group and ginsenoside-induced BMSCs group,with 15 rats in each group.The model group and the normal group were injected with 1 mL of cell culture medium from the tail vein and the BMSCs group was injected with 1 mL of BMSCs suspension (cell concentration:2.0×109/L).The ginsenoside-induced BMSCs group was injected with 1 mL of ginsenoside to induce differentiation of BMSCs (cell concentration 2.0×109/L).The solution was administered continuously for 10 days.The pathological conditions of liver tissue were observed, serum TBil,AST,ALT,TNF-α,IL-6 levels,Wnt7b,Wnt7a and Wnt2 gene expression in liver tissue.RESULTS:The normal group of rats had no necrosis,degeneration,neatly arranged,the structure of hepatic lobule was clear,and there was no inflammatory cell infiltration in the portal area.The hepatocytes in the model group were characterized by extensive necrosis,and all hepatocytes in the hepatic lobules were necrotic.The stent collapsed, and there were a large number of granulocytes, monocytes and lymphocytes infiltrated in the portal area and surrounding areas.The residual hepatocytes were degenerated,swollen and accompanied by cholestasis.The BMSCs group and ginsenoside-induced BMSCs group showed that the hepatic lobule structure became more intact.The number of hepatocyte necrosis and degeneration was reduced,and there was a little inflammatory cell infiltration in the portal area. The ginsenoside-induced BMSCs group was superior to BMSCs.Compared with the normal group,serum TBil,AST,ALT,IL-6 and TNF-α level in the model group increased. Compared with the model group, serum TBil,AST,ALT,IL-6 and TNF-α level in the BMSCs group and ginsenoside-induced BMSCs group decreased.Compared with BMSCs group,the levels of serum TBil,AST,ALT,IL-6 and TNF-α in ginsenoside-induced BMSCs group were significantly lower (P<0.05).Compared with the normal group,the relative expression of Wnt7b,Wnt7a and Wnt2 mRNA in the liver tissue of the model group was decreased.Compared with the model group,the relative expression of Wnt7b,Wnt7a and Wnt2 mRNA in the BMSCs group and ginsenoside-induced BMSCs group increased.Compared with BMSCs group,the relative expression of Wnt7b,Wnt7a and Wnt2 mRNA in the liver tissues of rats in ginsenoside-induced BMSCs group increased,the difference was statistically significant (P<0.05). CONCLUSION:Ginsenoside-induced BMSCs can significantly improve liver function in ALF rats,and its mechanism may be related to activating Wnt/β-catenin signaling pathway to accelerate liver regeneration.

Key words: acute liver failure, bone marrow mesenchymal stem cells, ginsenosides, liver tissue regeneration