[Role of Janus kinase/signal transducer and activator of transcription pathway in mediating mRNA expression of high mobility group box1 protein in the liver in septic rats].

OBJECTIVE: To investigate the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in mediating mRNA expression of high mobility group box 1 protein (HMGB1) in the liver in septic rats. METHODS: Using a sepsis model of cecal ligation and puncture (CLP), 98 male Wistar rats were randomly divided into normal control group (n=10), CLP group (n=40), AG490 treatment group (n=24), and Rapamycin (RPM) treatment group (n=24). At serial time points animals in each group were sacrificed, and blood as well as hepatic tissue samples were harvested to determine HMGB1 mRNA expression and serum aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) contents. RESULTS: Compared with normal controls, HMGB1 mRNA levels were significantly increased in the liver during 6-48 hours after CLP (P<0.01), and serum AST and ALT contents were significantly elevated at different time points respectively (P<0.05 or P<0.01). Treatment with AG490 and RPM could markedly inhibit HMGB1 mRNA expression in the liver at 24 hours, 48 hours, 6 hours and 24 hours after CLP, respectively. In addition, compared to CLP group, serum AST and ALT contents in both treatment groups could be markedly reduced at various intervals after CLP (P<0.05 or P<0.01). CONCLUSION: These data suggest that the activation of JAK/STAT pathway might be involved in mediating up-regulation of HMGB1 mRNA expression in the liver in CLP-induced sepsis. Treatment with inhibitors of JAK/STAT pathway could markedly down-regulate HMGB1 mRNA expression and attenuate acute liver injury associated with sepsis.