A murine model of LPS/D-gal-induced acute hepatitis and alterations in mTOR signaling / 中国实验动物学报

ABSTRACT

Objective To explore the changes of mTOR signaling in LPS/D-gal-induced acute hepatitis in mice . Methods Twenty-six healthy adult female ICR mice were divided into two groupsthe control group and experimental group, 13 mice in each group .LPS/D-gal was used to induce acute hepatitis in the mice .The survival of mice was moni-tored within 24 hours after LPS/D-gal challenge .At 6 hours after challenge , samples of serum and liver tissue were collect-ed for further analysis.Results Injection of LPS/D-gal resulted in acute death of the mice within 24 hours.At 6 hours post LPS/D-gal injection , the blood levels of ALT and AST were significantly increased .The mRNA expression of inflammatory cytokines Tnfa and Il6 was up-regulated in LPS/D-gal-induced hapatitis , in which DNA fragmentation and activation of caspase-3 were subsequently observed .Immunoblot analysis showed that both mTOR pathway and NF-κB pathway were ac-tivated.Unexpectedly , inhibition of mTOR signaling could neither decrease the apoptosis in the liver nor increase the sur -vival of mice .Conclusions The results of the present study indicate that mTOR signaling may play pleiotropic roles in the pathogenesis of LPS/D-gal-induced hepatitis .