Effects of Wogonin on liver fibrosis in cirrhotic rats by regulating the Hippo/YAP signaling pathway
Objective To investigate the effects of Wogonin(Wog)on liver fibrosis in cirrhotic rats by regulating the Hippo/Yes associated protein(YAP)signaling pathway.Methods The rats were divided into blank control(with intraperitoneal injection of equal volume of saline solution+intragastric administration of equal volume of saline solution),model(with intraperitoneal injection of equal volume of saline solution+intragastric administration of equal volume of saline solution),positive control(with intragastric administration of 0.8 g/kg Compound Biejia Ruangan Tablets solution),low-,medium-,and high-dose(with intraperitoneal injection of 7,14,28 mg/kg Wog)Wog groups,with 12 rats in each group.Except for blank control group,the other groups were injected intraperitoneally with carbon tetrachloride in aqueous solution to construct cirrhosis models.After modeling,all rats were treated with corresponding drugs,for consecutive 4 weeks.The serum liver function indicators of rats including alanine aminotransferase(AST)and aspartate aminotransferase(ALT)were measured;ELISA was used to test serum fibrosis indicators including type Ⅲ procollagen(PCⅢ),hyaluronic acid(HA),and laminin(LN);Hatmatoxylin-eosin(HE),Masson and immunohistochemical staining were performed to observe the degree of liver fibrosis in cirrhotic rats;Ishak score was used to determine the degree of liver tissue fibrosis,the collagen volume fraction(CVF),and the positive expressions of collagen-I(COL-Ⅰ)and collagen-Ⅲ(COL-Ⅲ);Western blot was used to determine the expression levels of α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),and Hippo/YAP signaling pathway in liver tissue.Results Compared with blank control group,the expressions of AST,ALT,PCⅢ,HA,LN,Ishak score,CVF,COL-I,COL-Ⅲ,α-SMA,and TGF-β1 in model group were higher(P<0.05),the expressions of phosphorylation(p)-large tumor suppressor gene 1(LATS1)/LATS1 and p-YAP/YAP were lower(P<0.05);compared with model group,the expressions of AST,ALT,PCⅢ,HA,LN,Ishak score,CVF COL-I,COL-Ⅲ,α-SMA,and TGF-β1 in low-,medium-,and high-dose Wog groups and positive control group were lower(P<0.05),the expressions of p-LATS1/LATS1 and p-YAP/YAP were higher(P<0.05).The levels of AST,ALT,PCⅢ,HA,LN,Ishak score,CVF,COL-Ⅰ,COL-Ⅲ,α-SMA and TGF-β1 in all dose Wog groups decreased with the increase of dose(P<0.05).While the levels of p-LATS1/LATS1 and p-YAP/YAP increased with the dose increasing(P<0.05).Conclusion Wog may improve liver fibrosis in cirrhotic rats by inhibiting the activation of Hippo/YAP signaling pathway.
liver cirrhosisliver fibrosisWogoninHippo signaling pathwayYes-associated protein
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