Effects of halofuginone on hepatic fibrosis in rats and their mechanism
10.7501/j.issn.0253-2670.2013.23.017
- Author:
Jie LIANG
1
Author Information
1. Department of Immunology
- Publication Type:Journal Article
- Keywords:
α-SMA;
Col I;
Concanavalin A;
Halofuginone;
Hepatic fibrosis;
TGF-β1
- From:
Chinese Traditional and Herbal Drugs
2013;44(23):3352-3358
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investagate the protective effects of halofuginone against liver injury induced by concanavalin A (Con A) in rats and their mechanism. Methods: Rats were divided into control (G1, 8), model (G2, 14), low- (5 mg/kg, G3, 14) and high-dose (10 mg/kg, G4, 14) halofuginone groups. The rats in G1 were iv injected with 300 μL PBS from tail vain once a week, the rats in other three groups were iv injected with 12.5 mg/kg Con A (in 300 μL PBS) once a week for eight consecutive weeks. Halofuginone was given in the diet for rats in G3 and G4 after molding and continuous administration for eight weeks after the rats were weighted and then were put to execution. The biochemical analysis was used to determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), and album protain (ALB) in serum while enzyme-linked immuno sorbent assay (ELISA) was applied for detecting transforming growth factor β1 (TGF-β1), hyaluronic acid (HA), and procollagen III (PC-III) levels in serum. HE and Masson's trichrome stainings were conducted in liver tissue to observe the pathological variations. Grades of hepatic fibrosis were evaluated according to SSS system. Sirus and immunohistochemical stainings were executed for detecting the deposition and protein expression of collagen 1 (Col I) in liver tissue. Results: Compared with the G2, halofuginone could decrease the levels of ALT, AST, TP, ALB, TGF-β1, HA, and PC-III in serum obviously (P < 0.05, 0.01). Halofuginone could improve the liver pathological variations of fibrotic rats obviously (P < 0.05, 0.01) and reduce the score of hepatic fibrosis significantly (P < 0.05, 0.01). Halofuginone treatment could reduce the deposition and expression of Col I protein (P < 0.05, 0.01). Conclusion: Halofuginone could attenuate the Con A-induced immunological liver injury and the fibrosis level in rats. The mechanisms possibly contribute to down-regulating the deposition and expression of Col I protein in liver of rats.
