Tauroursodeoxycholic Acid Alleviates The Hepatic Ischemia Reperfusion Injury By Suppressing The Function Of Kupffer Cells In Rats

Objective:The aim of this study is to investigate the protective effect and its mechanism of TUDCA against the hepatic ischemia reperfusion(IR)injury.Methods:Kupffer cells were isolated,cultured and treated with TUDCA or phosphate buffer solution(PBS)for 24 h,then the viability were examined.Inflammatory factors,IRE1?/TRAF2/NF-?B pathway activity were detected.Male SD rats were intraperitoneal injected with tauroursodeoxycholic acid(400mg/kg)or saline solution,once per day for3 days before the operation,then the model of hepatic I/R injury was established.Each group of the blood and liver sample was collected at 3,6,24 h after operation,respectively.The pathology change of liver,liver function,hepatocyte apoptosis and the proinflammatory factors were detected.Results:Treated by TUDCA,the secretion of IL-1?,IL-6 and TNF-? in active Kupffer cells were decreased(p<0.05).The expression of IRE1?,TRAF2,p-IKK?,p-I?B,p-P65 and the intranuclear expression of P65 were significantly decreased(p < 0.05).Furthermore,in our model,TUDCAalleviated the hepatic I/R injury,level of liver function markers(p<0.05),hepatocyte apoptosis(p<0.05)in vivo.TUDCA suppressed the secretion of IL-1??IL-6?TNF-?(p<0.05)and down-regulated the expression of IRE1?,TRAF2,p-IKK?,p-I?B,p-P65(p<0.05).Conclusion:TUDCA can effectively alleviate the hepatic IR injury by down-regulating the activity of IRE1?/TRAF2/NF-?B pathway to suppress the function of KCs.