Necroptosis contributes to deoxynivalenolinduced liver injury and inflammation in weaned piglets  

作　　者：Qilong Xu Hanqiu Gong Mohan Zhou Junjie Guo Shaokui Chen Kan Xiao Yulan Liu 

机构地区：[1]Hubei Key Laboratory of Animal Nutrition and Feed Science,Wuhan Polytechnic University,Wuhan 430023,China

出　　处：《Journal of Animal Science and Biotechnology》2025年第1期182-192,共11页畜牧与生物技术杂志(英文版)

基　　金：Project of National Natural Science Foundation of China(U22A20517 and 32272906).

摘　　要：Background The aim of this study was to investigate the role of necroptosis in deoxynivalenol(DON)-induced liver injury and inflammation in weaned piglets.Methods In Exp.1,12 weaned piglets were divided into 2 groups including pigs fed basal diet and pigs fed diet contaminated with 4 mg/kg DON for 21 d.In Exp.2,12 weaned piglets were divided into 2 groups including con-trol piglets and piglets given a gavage of 2 mg/kg body weight(BW)DON.In Exp.3,24 weaned piglets were used in a 2×2 factorial design and the main factors including necrostatin-1(Nec-1)(DMSO or 0.5 mg/kg BW Nec-1)and DON challenge(saline or 2 mg/kg BW DON gavage).On 21 d in Exp.1,or at 6 h post DON gavage in Exp.2 and 3,pigs were killed for blood samples and liver tissues.Liver histology,blood biochemical indicators,and liver inflamma-tion and necroptosis signals were tested.Results Dietary or oral gavage with DON caused liver morphological damage in piglets.Dietary DON led to hepato-cyte damage indicated by increased aspartate transaminase(AST)activity and AST/alanine aminotransferase(ALT)ratio,and DON gavage also caused hepatocyte damage and cholestasis indicated by increased AST and alkaline phosphatase(AKP)activities.Dietary DON caused liver necroptosis indicated by increased protein abundance of total receptor interacting protein kinase 3(t-RIP3)and total mixed lineage kinase domain-like protein(t-MLKL).Moreover,DON gavage increased mRNA expression of interleukin(IL)-6 and IL-1βin liver.DON gavage also induced liver necroptosis demonstrated by increased protein abundance of t-RIP3,phosphorylated-RIP3(p-RIP3),t-MLKL and p-MLKL.However,pretreatment with Nec-1,a specific inhibitor of necroptosis,inhibited liver necroptosis indi-cated by decreased protein expression of t-RIP3,p-RIP3,t-MLKL and p-MLKL.Nec-1 pretreatment reduced liver morphological damage after DON gavage.Pretreatment with Nec-1 also attenuated liver damage induced by DON indicated by decreased activities of AST and AKP.Furthermore,Nec-1 pretreatment inhibited liver mRNA expression

关 键 词：DEOXYNIVALENOL Liver damage NECROPTOSIS Necrostatin-1 PIGS 

分 类 号：S858.28[农业科学—临床兽医学]