Upregulated IRF9 promotes cell apoptosis of hyperlipidemia acute pancreatitis with heart injury by regulating SIRT1

Abstract

Hyperlipidemia acute pancreatitis (HLAP) is a significant cause of AP, characterized by recurrent attacks, more complications and high incidence and mortality. HLAP is often accompanied by single or multiple organ damage. Negative regulation of interferon-regulatory factor 9 (IRF9) on sirtuin-1 (SIRT1) contributes to a range of diseases. However, the function of IRF9 and SIRT1, and the relationship of the two in HLAP with heart injury remain to be illustrated so far. Animal models of HLAP were set up by feeding with high-fat chow and subsequently injecting 20% L-arginine intraperitoneally. The degree of pancreas and heart tissue injury was evaluated. Heart cell apoptosis was assayed by the TUNEL technique. IRF9, SIRT1, p53 and acetylated p53 (Ac-p53) expression levels were measured by qRT-PCR and western blot. The correlation between SIRT1 and IRF9 expression levels was analyzed. Results showed that the damage degree in rat pancreas and heart tissues of AP and HLAP group was more distinctly and heart cell apoptosis was elevated. Pancreas, heart injury and cell apoptosis of the HLAP group were more remarkable than that of the AP group. Apparent increases of IRF9 and Ac-p53/p53 expression and a marked drop of SIRT1 expression were observed in the AP and HLAP group rather than NC and HLNC group. IRF9 and Ac-p53/p53 expression levels of the HLAP group were markedly raised compared with the AP group. SIRT1 expression of the HLAP group was obviously lower than that of the AP group. There was an inverse correlation between the decrease of SIRT1 and the increase of IRF9 in AP and HLAP groups. Based on the above findings, we drew a conclusion that in pancreatitis with heart injury, upregulated IRF9 inhibited SIRT1 expression, elevated the acetylation of p53, and increased myocardial cell apoptosis. Hyperlipidemia further exacerbated pancreas and heart injury and accelerated myocardial cell apoptosis. These results would furnish an experimental and theoretical basis to diagnose and therapy diseases.