Elevated IRF9 raised cell apoptosis and tissue damages through suppressing SIRT1 in hyperlipidemia acute pancreatitis with liver injury

Abstract

Abstract Background Hyperlipidemia is a vital etiology of acute pancreatitis (AP), 12 to 20% of which have a history of hyperlipidemia. Multiple organ failure is the major cause of the high mortality rate of AP. Liver injury has been discovered in 80% of AP patients. The relationship and role of IRF9 and SIRT1 have not been presented in AP and hyperlipidemia AP (HLAP) with liver injury. This investigation was designed to explore the function and relationship of IRF9 and SIRT1. Methods HLAP model in vivo was performed by feeding high-fat forage and induced by peritoneal injection with 20% L-arginine. The severity of pancreas and liver tissues was assessed. Cell apoptosis in the liver was determined by the TUNEL experiment. IRF9, SIRT1, p53, and acetylated p53 (Ac-p53) expression levels in liver tissues were detected by qRT-PCR and Western blot. The association of IRF9 expression with SIRT1 levels was evaluated. The relevance of triglyceride level to tissue damage was analyzed. Results Our observation exhibited more distinct liver damage, a large number of hepatic cell apoptosis, marked raised IRF9, Ac-p53, and sharply dropped SIRT1 in the AP and HLAP groups. Compared with other groups, HLAP showed the most significant changes in liver injury, hepatic cell apoptosis, protein, and mRNA levels. The declined expression of SIRT1 was correlated with the elevated expression of IRF9. The damage of the pancreas and liver exacerbated with the increase in triglyceride levels. Conclusion Elevated IRF9 in pancreatitis with liver injury raised cell apoptosis and tissue damage by decreasing SIRT1 expression.

Keywords

• IRF9
• SIRT1
• HLAP
• Liver injury
• Apoptosis