Wogonin reduces the degree of fibrosis in cirrhotic rats by regulating Hedgehog-YAP signal pathway
Objective:To investigate the influence of Wogonin(Wog)on the degree of fibrosis in cirrhotic rats and its mechanism.Methods:The rats were divided into the control group,model group,Cym group(Hedgehog inhibitor group),and low,medium and high dose Wog group.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl transpeptidase(GGT),hyaluronic acid(HA),collagen type Ⅳ(CⅣ),laminin(LN)and procollagen type III(PCⅢ)were measured.Sirius red staining was used to observe the pathological morphology and degree of liver fibrosis.RT-qPCR was used to detect the expression of collagenⅠ(ColⅠ)and α-actin(α-SMA)in liver tissues.The activities of hydroxyproline(Hyp),superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissues were measured,and the expression levels of SMO,GLI2,SHH,YAP and p-YAP related proteins in Hedgehog-YAP pathway were detected by Western blotting.Results:Compared with the control group,the activities of ALT,AST,GGT,the contents of HA,CⅣ,LN and PCⅢ in serum,and the levels of ColⅠ and α-SMA mRNA,the contents of Hyp and MDA,and the expression of SMO,GLI2,SHH,and p-YAP/YAP in the model group were increased,while the activity of SOD in the model group was decreased.Compared with the model group,the activities of ALT,AST,GGT,the contents of HA,CⅣ,LN and PCⅢ in serum,and the levels of ColⅠ and α-SMA mRNA,the contents of Hyp and MDA,and the expression of SMO,GLI2,SHH,and p-YAP/YAP were reduced,and SOD levels were increased in the Cym and low,medium,and high-dose Wog groups.There was no significant difference in the above indicators between the Cym group and the high-dose Wog group.The liver tissue of the control group did not show an increase in fibrous tissue proliferation,while the liver tissue of the model group showed obvious collagen fiber proliferation and an increase in collagen staining area.Compared with the model group,the degree of collagen fiber proliferation in the liver tissue of the Cym and low,medium,and high-dose Wog groups was reduced,and the collagen staining area was decreased.There was no significant difference in the degree of collagen fiber proliferation between the Cym group and the high-dose Wog group.Conclusion:Wog may reduce the degree of liver fibrosis in cirrhotic rats and has a protective effect on rats with liver fibrosis models.The mechanism may be related to the inhibition of the Hedgehog-YAP signaling pathway by Wog.
Wogoninhedgehog-Yes associated protein 1 signal pathwaycirrhosishepatic fibrosishepatic functioncollagen