Effect of Physcion on Hepatic Fibrosis in Rats via Regulating Keap1/Nrf2 Signaling Pathway
Objective:To investigate the protective effect of physcion on hepatic fibrosis in rats by regulating the Keap1/Nrf2 signaling pathway.Methods:SD rats were randomly divided into model control group,colchicine 0.2 mg/kg group,and physcion 20 mg/kg and 40 mg/kg groups.Hepatic fibrosis model in rats was established by intraperitoneal injection of 40％ carbon tetrachloride-olive oil suspension.A normal control group was also set up.Starting from the 2nd day of modeling,each group was orally administered with corresponding drugs once a day for 8 weeks.Serum levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),albumin (ALB),total protein (TP),glutathione peroxidase (GSH-Px),catalase (CAT),malondialdehyde (MDA),superoxide dismutase (SOD),laminin (LN),hyaluronic acid (HA),type Ⅲ procollagen (PC-Ⅲ),and type Ⅳ collagen (Ⅳ-C) were measured using reagent kits.Liver tissues were subjected to HE and Masson staining to observe pathological changes,and Ishak scoring was performed.Immunohistochemistry was used to detect the positive expression of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in liver tissues.Western blot was conducted to detect the protein expression of Kelch-like ECH-associated protein 1 (Keap1),nuclear factor E2-related factor 2 (Nrf2),heme oxygenase-1 (HO-1),and NAD(P)H quinone oxidoreductase 1 (NQO1) in liver tissues.Results:Compared with the nor-mal control group,the model control group showed significantly increased serum levels of AST,ALT,ALP,HA,LN,PC-Ⅲ,and Ⅳ-C activities or content,significantly decreased ALB and TP content (P<0.01),significantly increased MDA content in liver homogenate (P<0.01),sig-nificantly decreased SOD,GSH-Px,and CAT activities or content (P<0.01),significantly increased inflammation and fibrosis scores in liver tissues (P<0.01),significantly upregulated expression of α-SMA,TGF-β1,and Keap1 in liver tissues (P<0.01),and significantly downreg-ulated expression of Nrf2,HO-1,and NQO1 proteins (P<0.01).Compared with the model control group,the physcion 20 mg/kg and 40 mg/kg groups showed significantly decreased serum levels of AST,ALT,ALP,HA,LN,PC-Ⅲ,and Ⅳ-C activities or content,significantly increased ALB and TP content (P<0.05 or P<0.01),decreased MDA content in liver homogenate (P<0.05 or P<0.01),significantly in-creased SOD,GSH-Px,and CAT activities or content (P<0.01),significantly decreased inflammation and fibrosis scores in liver tissues (P<0.05 or P<0.01),significantly downregulated expression of α-SMA,TGF-β1,and Keap1 in liver tissues (P<0.05 or P<0.01),and signifi-cantly upregulated expression of Nrf2,HO-1,and NQO1 proteins (P<0.05 or P<0.01).Conclusion:Physcion can improve liver function and oxidative stress indicators in liver fibrosis rats,alleviate the degree of hepatic fibrosis,and its mechanism may be related to the regulation of the Keap1/Nrf2 signaling pathway.
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