The Role And Mechanism Of IRF9 Negative Regulation On SIRT1 In Hyperlipidemia Acute Pancreatitis Associated With Kidney Injury

Objective Hyperlipidemic pancreatitis(HLAP)patients have more severe systemic inflammatory response.HLAP are more likely to cause multiple organ damage.Among them,acute kidney injury(acute kidney injury,AKI)is the most common,accounting for about 20%.The mortality of HLAP patients with AKI increases fivefold.Interferon regulatory factor 9(IRF9)is a negative regulator of silencing information regulatory protein 1(SIRT1)and plays an important role in multiple diseases.However,the role of IRF9 and SIRT1 in HLAP associated with kidney injury is unclear.This study is aimed to explore the role and function of interferon regulatory factor 9(IRF9)and sirtuin-1(SIRT1)in Hyperlipidemia acute pancreatitis associated with kidney injury,and provide theoretical guidance for disease diagnosis and treatment.Methods Sixty healthy adult male Sprague-Dawley rats(300-350 g),were randomly divided into four groups,including the normal control(NC)group(n=6),acute pancreatitis(AP)group(n=24),hyperlipidaemia control(HLAP)group(n=6)and hyperlipidemia acute pancreatitis(HLAP)group(n=24).The NC and AP group were fed with normal diet and the HLNC and HLAP group were fed with high fat diet.Blood lipids and cholesterols were measured in each group.When serum lipid and cholesterols in the HLNC and HLAP group were significantly higher than NC and AP group,20% L-arginine(1 ml/100 g)was injected to the AP group and the HLAP group,and normal saline(1 ml/100 g)was injected to the NC and HLNC group.Blood was taken from the heart tissue,and pancreatic and kidney tissues were dissected.Serum lipase,amylase(AMS),IL-1? and TNF-? were determined after injection 24 h.The pathological changes of pancreatic and kidney tissues were observed with light microscopes and the pathological section of pancreas tissues was scored by two blinded pathologists with expertise in pancreatic pathology for determining inflammation and necrosis severity of injury.The apoptosis of kidney tissue was determined by TUNEL staining,and the m RNA and protein expression levels of IRF9 and SIRT1 were detected by quantitative PCR assays and western blot.The protein expression level of p53 and acetylated p53 were determined by western blotting.Results 1)Compared with NC and HLNC group,serum lipase,amylase(AMS),IL-1? and TNF-? were elevated in AP and HLAP group.Pancreatic and kidney tissues injury were more serious and the apoptosis of kidney epithelial cells increased in AP and HLAP group.The m RNA and protein expression levels of IRF9 were up-regulated and SIRT1 were down-regulated in AP and HLAP group(P<0.05).And the down-regulation of SIRT1 was negatively correlated with the expression of IRF9(P<0.05).The expression of p53 and acetylated p53 were up-regulated(p<0.05).2)Compared with AP group,pancreatic and kidney tissues were more damaged and the apoptosis of kidney epithelial cells increased significantly in HLAP group.The m RNA and protein expression levels of IRF9 were higher and the down-regulation of SIRT1 was more obvious in HLAP group(P<0.05).Conclusion Hyperlipidemia aggravated pancreatic and kidney tissues injury.In the Hyperlipidemia pancreatitis associated with kidney injury,IRF9 might be a negative regulator of SIRT1,increased the expression of acetylated p53 and aggravated kidney tubular epithelial cell apoptosis.