Proteasome inhibitor bortezomib attenuates hepatic injury in the bile duct-ligated rats

Abstract

Objective To assess the protective effect of the proteasome inhibitor bortezomib on rat liver subjected to bile duct obstruction. Methods Thirty rats were divided randomly into three groups, which were sham-operation group (SO group), bile duct ligation control group (Con group) and bortezomib group (Bor group). All rats in the Con group underwent ligation of the common bile duct, and rats in the Bor group were given bortezomib intrabominally at-1 d, 4 d post-ligation of the common bile duct. All the rats were sacrificed at 7 d post-surgery. ALT, TB and TBA levels were determined. The expression of NF-κB p65 was assessed using immunohistological staining. RT-PCR was employed to detect TNF-α mRNA levels in liver samples. Results There was no significance in the levels of TB and TBA between Con and Bor groups. The ALT revel in the Bor group [(92.4±21.4)μmol/L]was significantly lower than that in the Con group [(145.7 ±33.5) μmol/L], P＜0.05. The positive staining rate of NF-κB p65 subunit in the Bor group showed significant lower value (11.6% ±2.7 % ) compared to that in the Con group (15.5 %±4.3 % ), P＜0.05. The expression ratio of TNF-α mRNA in the Bor group was 1.0± 0. 2, which also significantly lower than that in the Con group (1.3±0.4), P＜0. 05. Conclusion These data suggest that the proteasome inhibitor bortezomib reduces rat hepatocyte injury in the bile duct ligation by mechanisms associated with the inhibition of NF-κB as well as the attenuation of inflammation. Key words: Proteasome inhibitor; Bortezomib; Bile duct obstruction; Hepatic injury