Apolipoprotein A‐1 protected hepatic ischaemia–reperfusion injury through suppressing macrophage pyroptosis via TLR4–NF‐κB pathway

作者：Rui‐Xiang Chen, Wang‐Jie Jiang, Shuo‐Chen Liu, Ziyi Wang, Zhibo Wang, Tao Zhou, Yan‐An‐Lan Chen, Ji‐Fei Wang, Jiang Chang, Yi‐Rui Wang, Yao‐Dong Zhang, Xue‐Hao Wang, Xiangcheng Li, Chang Xian Li · 发表于：Liver International · 年份：2022 · DOI：10.1111/liv.15448 · 被引用次数：26 · 研究领域：Inflammasome and immune disorders、Mitochondrial Function and Pathology、Immune Response and Inflammation

BACKGROUND AND AIMS: Apolipoprotein A-1 (ApoA-1), the major apolipoprotein of high-density lipoprotein, plays anti-atherogenic role in cardiovascular diseases and exerts anti-inflammation effect in various inflammatory and infectious diseases. However, the role and mechanism of ApoA-1 in hepatic ischaemia-reperfusion (I/R) injury is unknown. METHODS: In this study, we measured ApoA-1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA-1 knockout mice, ApoA-1 mimetic peptide D-4F treatment mice and corresponding control mice to examine the effect of ApoA-1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study. RESULTS: The results showed that ApoA-1 expression was down-regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA-1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA-1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA-1 deficiency. Furthermore, the up-regulated pyroptosis process was testified to be mediated by ApoA-1 through TLR4-NF-κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D-4F...