Abstract: Objective To observe the effect of tauroursodeoxycholic acid (TUDCA) on hepatocytes apoptosisofspontaneoustype 2 diabetes mellitusdb/db mice and to explore its mechanism. Methods db/dband db/m (lean)mice were randomly divided into control groupsandTUDCA-treatedgroups.TUDCA 500mg/kg/day was given by gavage for 2 weeks in TUDCA-treated groups. The levels of fasting plasma glucose (FPG) and fasting insulinin serum and the levels of malondialdehyde (MDA), reactive oxygen species (ROS) and superoxide dismutase (SOD) in liver tissue were detected.Lipid deposition in liver tissue was detected by oil red O staining. Hepatocytes apoptosis in liver tissue was examined by TUNEL method. The transcription and expression levels of C-JUN and XBP-1 in liver tissue were examined by real-time PCR and western blotting method. The morphology and ultrastructure changes of liver tissue were observed by light microscope and transmission electron microscope. ResultCompared with lean control group, the levelsof FPG, aminotransferase, MDA and ROS were increased ; theexpression levels of C-JUN and XBP-1 were upregulated; lipid droplets and apoptosis of hepatocyteswere significantly increased in db/db control group(p<0.05). Compared withdb/db control group, the levels FPG, aminotransferase, MDA and ROS were decreased; theexpression levels of C-JUN and XBP-1 were downregulated; lipid droplets and apoptosis of hepatocyteswere significantly decreasedin db/dbTUDCA-treated group(p<0.05).ConclusionTUDCA can alleviatehepatic damage of type 2 diabetes mellitus db/db mice by inhibiting hepatocytesapoptosis. Its mechanism may be related to inhibiting oxidative stress reaction, and downregulatingtheexpression of C-JUN and XBP-1 gene.

Key words: tauroursodeoxycholic acid, apoptosis, hepatic damage, type 2 diabetes mellitus, db/db mice