Abstract:

Objective   To investigate the inhibitory effect of ursodeoxycholic acid (UDCA) on hepatocarcinogenesis of rats and explore its mechanism. Methods   The hepatocarcinoma was induced by diethylnitrosamine (DEN) .Seventyfive male wistar rats were randomly divided into the normal control group, the UDCA control group, the DEN group and two UDCA intervention groups. The DEN group and the UDCA intervention groups were given an intraperitoneal injection of 20mg/kg body weight of DEN.The normal control group and the UDCA control group were given a same dose of saline. At the same time, UDCA were separately given to the UDCA control group and the UDCA high and low dose groups according to 30mg/(kg·d), 30mg/(kg·d ) and 15(mg/kg·d), the normal control group and the DEN group was given equivalent physiological saline. Changes of body weight， liver weight， organ coefficient of liver， ALT， AST and AFP in serum were observed and detected． Real-time quantitative RT-PCR was used to detect DNA repair enzyme hMTH1 in rat livers. Results   Compared with those of the normal control group， body weights significantly decreased and liver weights， organ coefficients of liver， the activities of ALT， AST and the content of AFP in serum significantly increased in the DEN group(P<0.05)． Compared with those of the DEN group，all indicators were significantly improved in the UDCA intervention groups(P<0.05)． Compared with that of the normal control group, the expression of hMTH1 was significantly higher in the DEN group and the UDCA intervention group(P<0.05). But the expression of hMTH1 were significantly lower in UDCA intervention group compared with DEN group(P<0.05); the expression of hMTH1 was significantly lower in the UDCA high dose group compared with that of the UDCA low dose group(P<0.05). There was no difference between the UDCA control group and the normal control group. Conclusion   UDCA can inhibit the development of hepatocarcinoma induced by DEN and the expression of hMTH1, which is positively related to dosage. Its mechanisms may be that UDCA can inhibit oxidative stress.

Key words: Ursodeoxycholic acid； Liver neoplasms; Diethylnitrosamine; hMTH1； Rats， Wistar