Abstract: Objective To explore the impact of paricalcitol (Pal) on the oxidative stress-induced tight junction damage of mouse hepatocytes and its mechanism. Methods A model of cholestatic liver injury was created by routine bile duct ligation. The mice were randomly divided into control group (control), model group (BDL) and treatment group (BDL+Pal). HE staining microscopy was used to observe the morphological changes of liver tissues. The human hepatoma cell line HepG2 was cultured and divided into blank group, model group (400 μmol/L H₂O₂) and treatment group (400 μmol/L H₂O₂+20 nmol/L Pal). Western blot was used to examine the level of tight junction protein 1 (ZO-1), occludin, phosphorylated p65 (p-p65), phosphorylated ERK (p-ERK) and phosphorylated myosin II regulated light chain (p-MLC) protein were checked in each group. Results Compared with the control group, the level of p-p65, p-ERK and p-MLC in the model group was significantly increased (P＜0.000 1 or P＜0.01 or P＜0.001). The protein expression of ZO-1 and occludin was significantly decreased (P＜0.01). HE staining microscopy showed an increased hepatocyte necrosis and inflammatory cell infiltration. In contrast, the above levels in the treatment group showed an opposite trend relative to the model group. Conclusions Pal is able to alleviate the damage of hepatocyte tight junctions by inhibiting oxidative stress in cholestatic mice and HepG2 cells. Its mechanism is potentially related to the inhibition of reactive oxygen species and NF-κB/p65 and ERK signaling pathways.

Key words: paricalcitol, oxidative stress, cholestasis, liver injury