Effect of bone marrow mesenchymal stem cells transplantation on expression of high mobility group box 1 protein in rats with acute liver failure

Abstract

Objective To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on expression of high mobility group box 1 protein (HMGB1) in rats with acute liver failure (ALF). Method SD rats were randomly divided into three groups: control group, ALF group and BMSCs transplantation group. Specimens were harvested in each group at 12 h, 24 h and 72 h after ALF induction. Serum ALT and AST concentrations were determined, liver pathological changes were observed by HE staining, serum HMGB1 concentration detected by ELISA, and HMGB1 mRNA and protein in liver tissues examined by RT-PCR and immunohistochemistry respectively. Result The ALF models were successfully induced by D-GalN (900 mg/kg) and LPS (10 μg/kg) injection. Serum levels of ALT and AST in the ALF group were gradually increased with progression of the disease. As compared with the ALF group, significant improvement of liver function parameters and histological findings was observed in the transplantation group 72 h after transplantation (P<0.01). The serum HMGB1 concentrations, the HMGB1 mRNA expression and the HMGB1 protein expression in liver tissue of control group were lowered at all time points, and they increased with time in the ALF group. After BMSCs transplantation, the serum HMGB1 concentrations, the HMGB1 mRNA and protein expression decreased with time. All the differences between ALF group and BMSCs transplantation group at 24 h and 72 h after transplantation were statistically significant (P<0.01). At 24th h after transplantation, mortality rates of control group, ALF group, BMSC transplantation group were 0 (0/24), 33.3% (8/24) and 16.7% (4/24) respectively with the difference being statistically significant (χ2=21.098, P<0.01). Conclusion BMSCs transplantation can improve the liver function and pathological changes in rats with ALF, and decrease the expression of HMGB1. Key words: Mesenchymal stem cells, bone marrow; Liver failure, acute; High mobility group box 1 protein; Rat