Background/Aims: The translocation of bacteria and their lipopolysaccharides from the gut can promote fibrosis in cirrhotic patients. The aim of this study was to investigate the effects of rifaximin on hepatic fibrosis in a bile duct-ligated rat model.
Methods: The bile duct ligation (BDL) was carried out for eight days (acute injury model: sham-operated rats [G1], BDL rats [G2], and BDL rats treated with rifaximin [G3]) or 22 days (chronic injury model: sham-operated rats [G4], BDL rats [G5], and BDL rats treated with rifaximin [G6]). Rifaximin (50 mg/kg/day) was administered daily via gavage after BDL. Liver function, serum tumor necrosis factor-alpha (TNF-α), and hepatic hydroxyproline levels were measured. Moreover, a histological analysis of fibrosis contents was performed using sirius red stain. Results: In the acute injury model, the liver function and TNF-α level were not improved after the rifaximin treatment. The hydroxyproline levels (μg/g liver tissue) in G1, G2, and G3 were 236.4±103.1, 444.8±114.4, and 312.5±131.6, respectively; and fibrosis contents (%) were 0.22±0.04, 1.64±0.53, and 1.66±0.44, respectively. The rifaximin treatment did not ameliorate acute BDL-induced fibrosis. In the chronic injury model, the hydroxyproline levels in G4, G5, and G6 were 311.5±72.9, 1,110.3±357.9, and 944.3±209.3, respectively; and fibrosis contents (%) were 0.19±0.03, 5.04±0.18, and 4.42±0.68, respectively (G5 vs. G6, p=0.059). The rifaximin treatment marginally ameliorated chronic BDL-induced fibrosis. Recently, it has been suggested that there is a significant relationship between gut microbiome and liver disease.Given that the liver is the first extraintestinal organ that encounters venous blood from the small and large intestines via
신승각 등. 간섬유화와 리팍시민The Korean Journal of Gastroenterology Therefore, in this study, we investigated the effects of rifaximin on hepatic inflammation and fibrosis in a bile duct-ligated rat model of acute and chronic liver injury.
SUBJECTS AND METHODS
Materials and animal experimentsRifaximin was provided by Hanall Biopharma (Seoul, Korea
Bile duct ligationFor all surgical procedures, the rats were anesthetized by inhalation of 5 vol% isoflurane in 100% oxygen at a flow rate of 4 L/min for the induction and 2-3 vol% at 2 L/min for the maintenance. In the sham operated group, a midline incision in the abdomen was made using the sterile techniques. In the BDL and BDL-rifaximin groups, after a midline laparotomy of 1-2 cm, the common bile duct was identified, doubly ligated using 5-0 silk sutures, and transected at the level of 0.7-0.8 cm distal to the last bifurcation. The first ligature was made below the junction of the hepatic ducts, and the second ligature was made above the entrance to the pancreatic ducts. Finally, the common bile duct was resected between the double ligatures. Each animal received a subcutaneous injection of 10 mg/kg ketoprofen for 1 day and 5 mg/kg gentamicin for 3 days, after the surgery. Rats in the sham G1, BDL G2, and BDL-rifaximin G3 groups were sacrif...