Effect and its mechanism of Fuyuan Huoxue Decoction on TGF-β1/Smad3 and TGF-β1/p38 pathway against liver fibrosis in mice
Objective:To explore the effect and mechanism of Fuyuan Huoxue Decoction(FYHX)on the effect of TGF-β1/Smad3 and TGF-β1/p38 pathway against liver fibrosis in mice.Methods:Twenty-four C57BL/6 male mice were divided into four groups:blank group,FYHX group,model group and CCl4+FYHX group.Mice in the model group and CCl4+FYHX group were intraperitoneally injected with 25%CCl4 corn oil solution,twice a week for 6 consecutive weeks.The blank group and the FYHX group were intraperitoneally injected with the same amount of com oil.Starting from the third week of modeling,the FYHX group and the CCl4+FYHX group were given FYHX by gavage every day for 4 weeks.HE staining,Sirius red staining,hydroxyproline(Hyp)content detection,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)levels were evaluated.Western Blot and immunohistochemical methods were used to detect α-smooth muscle agonist(α-SMA)and type Ⅰcollagen(Collagen-Ⅰ)protein expression;Western Blot was used to detect TGF-β 1,p38,p-p38,JNK,p-JNK,Smad3 and p-Smad 3 protein expression.Results:Compared with the blank group,fiber deposition in model group increased,and ALT and AST increased significantly(P<0.01).Compared with the model group,the degree of hepatocyte degeneration,necrosis,and fibrotic tissue proliferation in the CCl4+FYHX group was reduced,and the serum ALT,AST and Hyp content were significantly reduced(P<0.05);α-SMA,Collagen-Ⅰ,TGF-β 1,p-p38,p-Smad3 and p-JNK protein levels in liver tissue were significantly reduced(P<0.01).Conclusion:FYHX has good anti-CCl4-induced liver fibrosis in mice,and its mechanism of action may be related to the inhibition of hepatic stellate cell activation by TGF-β1/Smad3 and TGF-β1/p38 pathways.