Liver protection provided by ulinastatin in rats with liver fibrosis

Abstract

Objective To evaluate liver protection provided by ulinastatin in rats with liver fibrosis. Methods Fifty pathogen-free male Sprague-Dawley rats, weighing 180-220 g, aged 6-8 weeks, were randomly divided into 5 groups(n=10 each)using a random number table: control group(group C), carbon tetrachloride(CCl4)group, low-dose ulinastatin group(group L), medium-dose ulinastatin group(group M), and high-dose ulinastatin group(group H). Hepatic fibrosis was produced by subcutaneous injection of 50% CCl4 peanut oil solution two times a week for 8 weeks.After hepatic fibrosis was produced(at 9th week), ulinastatin 2.5×104, 5.0×104 and 10.0×104 U/kg were injected via the caudal vein in L, M and H groups, respectively, once a day for 7 days.Blood samples were collected after 24 h of fast on 8th day for determination of serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)concentrations by ELISA.The rats were then sacrificed and livers were removed for microscopic examination of pathologic changes with light microscope.The expression of interleukin-1β(IL-1β), IL-2, IL-6, IL-8, Toll-like receptor 4(TLR4), and tumor necrosis factor-alpha(TNF-α)mRNA and protein was detected by RT-PCR and Western blot. Results Compared with group C, the serum AST and ALT concentrations were significantly increased in CCl4, L and M groups, the expression of IL-1β, IL-2, IL-6, IL-8, TLR4 and TNF-α mRNA and protein was up-regulated in CCl4 group, and no significant change was found in the parameters mentioned above in group H. Compared with group CCl4, the serum AST and ALT concentrations were significantly decreased in M and H groups, no significant change was found in the serum AST and ALT concentrations in group L, and the expression of IL-1β, IL-2, IL-6, IL-8, TLR4 and TNF-α mRNA and protein was down-regulated in group H. The pathologic changes of hepatic tissues were attenuated in M and H groups as compared with group CCl4.The pathologic changes of hepatic tissues were almost recovered to the normal structure in group H. Conclusion Ulinastatin can produce liver protection in rats with liver fibrosis. Key words: Trypsin inhibitors; Liver fibrosis