Activation of NLRP3 Inflammasome via Drp1 Overexpression in Kupffer Cells Aggravates Ischemia-reperfusion Injury in Hepatic Steatosis

作     者：Lu Zhang Mingfu Wang Ran An Jun Dai Shujun Liu Ming Chen Haoran Ding 

作者机构：Department of Hepatobiliary SurgeryAffiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsuChina Surgery Department IZhangjiagang Traditional Chinese Medicine HospitalSuzhouJiangsuChina Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Wannan Medical CollegeWuhuAnhuiChina Department of Hepatobiliary SurgeryNanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineSchool of PharmacyNanjing University of Chinese MedicineNanjingJiangsuChina 

出 版 物：《Journal of Clinical and Translational Hepatology》 (临床与转化肝病杂志（英文版）)

年 卷 期：2023年第11卷第5期

页      面：1069-1078页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：Drp1 Kupffer cells NLRP3 Hepatic steatosis Ischemia-reperfusion 

摘      要：Background and Aims:Donors with fatty livers are considered to address the shortage of livers for transplantation,but those livers are particularly sensitive to ischemia-reperfusion injury(IRI),and an increased incidence of graft failure is *** cells account for 20–35%of liver nonparenchymal cells,and have been shown to participate in the process of IRI and inflammatory reactions of hepatic ***-like receptor thermal protein domain-associated protein 3(NLRP3)is an intracellular sensor activated by Kupffer cells to promote generation and participates in ***-associated protein 1(Drp1)is one of the main proteins regulating mitochondrial division and exacerbates IRI by affecting mitochondrial *** mechanism of interaction of Kupffer cells with Drp1 and NLRP3 to aggravate IRI has not been ***:A mouse model of hepatic steatosis was established by feeding the mice with a high-fat *** vitro experiments were performed using AML12 normal mouse liver cells and RAW264.7 mononuclear macrophage cells cultured in medium with palmitate and oleic *** blotting and immunohistochemical(IHC)staining were used to detect the expression of NLRPP3 and Drp1 in IRI in the control and high-fat diet *** expression of F4/80+cells during IRI in hepatic steatosis was verified by IHC staining,and the role of NLRPP3 and Drp1 in Kupffer-cell mediated IRI was investigated by targeting Drp-1 ***:Drp1 and NLRP3 expression was increased during IRI in hepatic steatosis,and the expression of Drp1 and NLRP3 were decreased after the elimination of Kupffer *** indicated Kupffer cells were involved in the process of IRI in hepatic steatosis through the action of Drp1 and *** Drp1 inhibition,liver function was restored and NLRP3 expression level was ***:Kupffer cells aggravated IRI in hepatic steatosis via NLRP3 and ***1 inhibitors might be useful as specific therapeutics to alleviate IRI