Effect of interferon-α on rat liver fibrosis induced by CCl(4).
10.3969/j.issn.1672-7347.2011.03.009
- Author:
Yanyan LI
1
;
Huixiang YANG
Author Information
1. Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Carbon Tetrachloride;
toxicity;
Connective Tissue Growth Factor;
genetics;
metabolism;
Hepatic Stellate Cells;
drug effects;
metabolism;
Interferon-alpha;
therapeutic use;
Liver Cirrhosis, Experimental;
chemically induced;
drug therapy;
metabolism;
Male;
RNA, Messenger;
genetics;
metabolism;
Random Allocation;
Rats;
Rats, Wistar;
Tissue Inhibitor of Metalloproteinase-1;
genetics;
metabolism;
Transforming Growth Factor beta1;
genetics;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2011;36(3):243-248
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the curative effect and the underlying mechanism of interferon-α (IFN-α) on rat liver fibrosis induced by CCl(4).
METHODS:Forty-five Wistar male rats were randomly divided into 3 groups: a normal control group (n=15), a liver fibrosis group (n=15) and a IFN-α treatment group (n=15). The rats of the control group and the liver fibrosis group received peanut oil (0.2 mL/100 g body weight), twice a week for 8 weeks. The rats of the liver fibrosis group and the IFN-α treatment group were received intraperitoneal injection of 50% CCl(4) (CCl(4):peanut oil=1:1, 0.2 mL/100 g body weight, ip) or IFN-α (CCl(4):peanut oil=1:1, 0.2 mL/100 g body weight, ip), twice a week for 8 weeks. In the 9th week, the rats of IFN-α treatment group were switch to receive IFN-α at 100 000 units (s.c.) per day for 3 weeks. The rats were all sacrificed in the 11th week. Pathological changes of liver, semi-quantitative scoring of rat liver was observed. Tissue hydroxyproline, the mRNA expression of Collagen I, Collagen III, transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), a-smooth muscle actin (α-SMA), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) of rat liver was detected. The protein expression of MMP-9 and TIMP-1 also was detected.
RESULTS:Semi-quantitative scoring of inflammation,semi-quantitative scoring of liver fibrosis, hydroxyproline and collagen in the IFN-α treatment group were significantly lower than those in the liver fibrosis group (all P<0.05). The mRNA expression of TGF-β1, CTGF, α-SMA and TIMP-1, and the protein expression of TIMP-1 in the IFN-α treatment group were significantly lower than those in the liver fibrosis group (all P<0.05). But there was no significant difference in MMP-9 between the IFN-α treatment group and the liver fibrosis group.
CONCLUSION:IFN-α can decrease the liver fibrogenesis induced by CCl(4) in rats and reduce liver inflammation response. The anti-fibrosis effect of IFN-α may be related to decrease in TGF-β1, CTGF and TIMP-1 expression and to inhibiting of the hepatic satellite cells' activation and extracellular matrix synthesis.
