PPARβ/δ activation protects against hepatic ischaemia–reperfusion injury

作者：Baolin Qian, Chaoqun Wang, Xiaozhuang Li, Panfei Ma, Liqian Dong, Benqiang Shen, Huibo Wu, Nana Li, Kai Kang, Yong Ma · 发表于：Liver International · 年份：2023 · DOI：10.1111/liv.15760 · 被引用次数：10 · 研究领域：Organ Transplantation Techniques and Outcomes、Peroxisome Proliferator-Activated Receptors、Cardiac Ischemia and Reperfusion

BACKGROUND AND AIMS: Hepatic ischaemia/reperfusion injury (HIRI) is a pathophysiological process that occurs during the liver resection and transplantation. Reportedly, peroxisome proliferator-activated receptor β/δ (PPARβ/δ) can ameliorate kidney and myocardial ischaemia/reperfusion injury. However, the effect of PPARβ/δ in HIRI remains unclear. METHODS: Mouse hepatic ischaemia/reperfusion (I/R) models were constructed for in vivo study. Primary hepatocytes and Kupffer cells (KCs) isolated from mice and cell anoxia/reoxygenation (A/R) injury model were constructed for in vitro study. Liver injury and inflammation were investigated. Small molecular compounds (GW0742 and GSK0660) and adenoviruses were used to interfere with PPARβ/δ. RESULTS: We found that PPARβ/δ expression was increased in the I/R and A/R models. Overexpression of PPARβ/δ in hepatocytes alleviated A/R-induced cell apoptosis, while knockdown of PPARβ/δ in hepatocytes aggravated A/R injury. Activation of PPARβ/δ by GW0742 protected against I/R-induced liver damage, inflammation and cell death, whereas inhibition of PPARβ/δ by GSK0660 had the opposite effects. Consistent results were obtained in mouse I/R models through the tail vein injection of adenovirus-mediated PPARβ/δ overexpression or knockdown vectors. Furthermore, knockdown and overexpression of PPARβ/δ in KCs aggravated and ameliorated A/R-induced hepatocyte injury, respectively. Gene ontology and gene set enrichment analysis showed that PPARβ/δ deleti...