Effect of activated farnesoid X receptor on apoptosis and liver damage in autoimmune hepatitis

Abstract

Objective To analyze the hepatoprotective and anti-apoptotic effects of farnesoid X receptor (FXR) in autoimmune hepatitis (AIH). Methods Total of 60 female C57BL/6 mice were divided into four groups randomly: the concanavalin A (ConA) model group, the chenodeoxycholic acid (CDCA) group, the CDCA+ ConA group and the normal control group, with 15 mice in each group.Blood samples of mice collected from retro-orbital venous plexus and were obtained to detect levels of aminotransferase and inflammatory cytokines.The liver specimens were collected, and the histopathological examination and detection were performed by HE staining.The cell apoptosis was assessed by the terminal deoxynucleotidase-transferase-mediated dUTP nick end labeling (TUNEL) method.The expression levels of apoptosis-related genes and proteins were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot respectively. Results The increase of transaminase activity and inflammatory cytokines levels were detected in ConA-treated mice.Compared with control group, the expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin (IL)-4 and IL-2 were increased in ConA-treated mice (F values were 18.764, 24.377, 24.573 and 26.482 respectively, all P values <0.05). The mice pretreated with the FXR agonist CDCA were more resistant to ConA hepatitis.Compared to the ConA group, the expression level of alanine aminotransferase/aspartate aminotransferase was significantly lower (t=13.595, P<0.05). The mRNA level of FXR in ConA-induced hepatitis-induced liver samples was significantly down-regulated (t=6.846, P<0.05). The mRNA level of FXR in the CDCA group was significantly increased(t=17.841, P<0.05). Compared with the ConA group, the mRNA level of FXR in the CDCA+ ConA group was significantly lower at 4, 8 and 12 h (t values were 5.386, 14.485, 9.385 respectively, all P values <0.05). Conclusion FXR activation improves liver injury and inhibits inflammatory cytokines in ConA-induced hepatitis.FXR may be exert a protective effect on ConA-induced apoptosis. Key words: Autoimmune hepatitis; Concanavalin A-induced hepatitis; Farnesol X receptor; Cell apoptosis