Qi Shunli, Yan Qi, Wang Zhen, Liu Deng, Zhan Mengting, Du Jian, Chen Lijian
Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
Department of Anesthesiology, Tongling People's Hospital, Tongling 244000, China.
PPAR Res. 2022 Mar 21;2022:2212996. doi: 10.1155/2022/2212996. eCollection 2022.
Liver ischemia/reperfusion (I/R) injury is a primary complication in major liver surgery. Our previous study about proteome profiling has revealed that the PPAR signaling cascade was significantly upregulated during liver ischemia/reperfusion. To elucidate the potential mechanisms of PPAR involved in I/R injury, we used oleoylethanolamide (OEA), the peroxisome proliferator-activated receptor alpha (PPAR) agonist, in this study. We demonstrated a protective role of OEA on liver I/R injury by using a mouse model of partial warm ischemia-reperfusion and hypoxia-reoxygenation model of hepatocytes. These effects were caused by ameliorating liver damage, decreasing the level of serum ALT and AST, and reducing the apoptosis of hepatocytes. Furthermore, a mechanistic study revealed that OEA regulated endoplasmic reticulum (ER) stress by activating PPAR, thereby reducing ER stress-associated apoptosis to attenuate liver I/R injury. Briefly, these data first proposed that OEA-mediated PPAR activation could be an effective therapy against hepatic ischemia/reperfusion injury.
肝脏缺血/再灌注（I/R）损伤是肝脏大手术中的主要并发症。我们之前关于蛋白质组分析的研究表明，在肝脏缺血/再灌注期间，过氧化物酶体增殖物激活受体（PPAR）信号级联反应显著上调。为了阐明PPAR参与I/R损伤的潜在机制，在本研究中我们使用了过氧化物酶体增殖物激活受体α（PPAR）激动剂油酰乙醇胺（OEA）。通过使用部分肝脏热缺血-再灌注小鼠模型和肝细胞缺氧-复氧模型，我们证明了OEA对肝脏I/R损伤具有保护作用。这些作用是通过改善肝脏损伤、降低血清谷丙转氨酶（ALT）和谷草转氨酶（AST）水平以及减少肝细胞凋亡而产生的。此外，一项机制研究表明，OEA通过激活PPAR调节内质网（ER）应激，从而减少与ER应激相关的凋亡，减轻肝脏I/R损伤。简而言之，这些数据首次表明，OEA介导的PPAR激活可能是治疗肝脏缺血/再灌注损伤的有效方法。
