Effect and regulatory mechanism of PPAR-γ agonists rosiglitazone on hepatocytes of Sprague Dawley rats with severe acute pancreatitis / 中华肝胆外科杂志

ABSTRACT

Objective:To study the effect of peroxisome proliferator activated receptor- γ (PPAR-γ) agonists rosiglitazone on the hepatocytes of Sprague Dawley (SD) rats with severe acute pancreatitis (SAP) and the regulatory mechanism.Methods:Seventy two healthy male SD rats, weighing 255-315 g, aged 49-56 days, were randomly divided into SAP model group ( n=24, SAP model preparation), rosiglitazone group ( n=24, rosiglitazone intravenous injection after SAP model preparation) and sham operation group ( n=24, normal saline injection only). After 6 h, 12h and 24 hours of injection, 8 rats were treated at each time point. HE staining was used to study the liver tissue structure and detect the levels of serum tumor necrosis factor-α(TNF-α), interleukin (IL) -1β, IL-6, AST, ALT and lactate dehydrogenase (LDH) in the rats. Western blot was used to detect the expression of high mobility group box-1 protein (HMGB1), Janus activated kinase (JAK)2 and signal transducer and activator of transcription (STAT)3. Results:The levels of serum TNF-α , IL-1β, IL-6, AST, ALT, LDH in SAP model group and rosiglitazone group were significantly higher than those in the sham operation group (all P<0.05). IL-1β at 6, 12h and 24 h in rosiglitazone group was (226.5±52.1)ng/L, (458.2±82.3)ng/L, (556.4±83.4) ng/L, ALT was (158. 3±39.2) U/L, (235.0±44.6)U/L, (298.4±56.6) U/L, which was lower than that in SAP model group (443. 5±62.3) ng/L, (622.6±78.3) ng/L, (789.1±105.7) ng/L and (198.4±42.5)U/L, (253.8±47.0)U/L, (337.2±60.1) U/L, the differences were statistically significant (all P<0.05). AST and LDH in rosiglitazone group were also lower than those in SAP model group at each time point, and the differences were statistically significant (all P<0.05). HE staining showed that there were less inflammation, hemorrhage and necrosis in rosiglitazone group than those in SAP model group. Expression of STAT3 in liver of rosiglitazone group at 6 h, 12 h and 24 h was (0.22±0.03), (0.30±0.04), (0.31±0.06), lower than SAP model group (0. 28±0.04), (0.38±0.05), (0.40±0.06), the differences were statistically significant (all P<0.05). Expression of JAK2 and HMGB1 in rosiglitazone group at 12 h and 24 h was also lower than that in SAP model group (all P<0.05). Conclusion:PPAR-γ agonists rosiglitazone can protect the SAP rats suffering from hepatocyte injury and inflammation, through JAK2/STAT3 pathway.