Therapeutic Effects Of Quercetin On Early Inflammation In Hypertriglyceridemia-related Acute Pancreatitis And Its Mechanism

Objective:Lots of studies have reported that hypertriglyceridemia(HTG)intensifies the course of acute pancreatitis(AP)and aggravates inflammatory responses;however,the exact mechanism remains unclear.Endoplasmic reticulum stress(ERS)is a pathophysiological concept of AP explained at the cellular and biological level,especially the IRE1?-s XBP1 pathway,which is closely associated with lipid metabolism and inflammation.C/EBP? and C/EBP? are two nuclear transcription factors involved in lipid metabolism and inflammation;however,their role in AP has not been reported so far.Quercetin,a naturally occurring plant flavonoid abundantly present in fruits,vegetables and cereals,is considered to have beneficial biological activities,including anti-inflammatory,antioxidant,antitumor,anti-atherosclerotic properties,and it has been shown to play a protective role in many diseases.The aim of the present study was to investigate the therapeutic effects of different doses of quercetin on the early stage inflammation of HTG related AP in vivo and its possible mechanism.Methods:In vivo experiment,HTG related AP rat model was induced by a high-fat diet(HFD: 77% normal chow +3% cholesterol +20% lard,2weeks)and peritoneal injections of cerulein(50 ?g/kg,qh ?2).Quercetin(100,150,200 mg/kg)was administered by peritoneal injections after AP induction.9 hours after AP induction,the injury of the pancreas was assessed by plasma amylase level and pancreatic histological changes.Dynamic expression of IL-1?,IL-6,TNFa,NF-k B,endoplasmic reticulum stress related molecules IRE1? and s XBP1,and C/EBP?,C/EBP? were monitored by WLISA,Realtime PCR,Western Blot,Inmunohistochemistry and Immunofluorescence.Results:Quercetin intervention dose-dependently reduced plasma amylase level(P<0.001),attenuated pancreatic histopathological damage(P<0.05)and inhibited proinflammatory cytokines expression in HTG related AP rats.In addition,quercetin dose-dependently down-regulated genes and proteins expression levels of IRE1?,s XBP1,C/EBP? and C/EBP?.Conclusion:Quercetin attenuates the early stage inflammation of HTG related AP probably through amelioration of IRE1?-s XBP1 and C/EBP?,C/EBP?.