目的·探讨磷脂酰乙醇胺（phosphatidylethanolamine，PE）对巨噬细胞衰老及其衰老相关分泌表型的影响和分子机制，以及PE在肝损伤中的病理生理学意义。方法·利用阿霉素建立巨噬细胞衰老模型，并给予PE处理。通过腹腔联合注射PE和脂多糖构建小鼠肝损伤模型，观察PE对肝损伤的影响。采用衰老相关β-半乳糖苷酶（senescence-associated β- galactosidase，SA-β-gal）染色，结合实时荧光定量PCR、Western blotting等检测细胞周期抑制蛋白p21、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白介素-6（interleukin-6，IL-6）等衰老标志物及衰老相关分泌表型生物活性因子的表达水平。通过RNA测序结合基因本体论（Gene Ontology，GO）细胞组分富集分析、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析、基因集变异分析（Gene Set Variation Analysis，GSVA）和基因集富集分析（Gene Set Enrichment Analysis，GSEA）筛选PE促进巨噬细胞衰老的信号通路及分子机制。通过体内和体外实验检测内质网应激相关通路中肌醇需求酶1α（inositol requiring enzyme 1 α，IRE1α）、剪接型X盒结合蛋白1（spliced X box binding protein 1，XBP1s）、转录激活因子6（activating transcription factor 6，ATF6）、ATF4、C/EBP同源蛋白（C/EBP homologous protein，CHOP）的表达。结果·PE显著促进巨噬细胞衰老标志物SA-β-gal、p21、p16及衰老相关分泌表型生物活性因子的表达。RNA测序分析显示内质网应激参与PE促进衰老相关分泌表型表达的作用。进一步的实验表明，PE通过激活巨噬细胞内质网应激信号通路促进巨噬细胞衰老及衰老相关分泌表型表达。体内实验证实PE通过内质网应激加剧脂多糖诱导的小鼠肝损伤。结论·PE通过激活内质网应激信号通路，促进巨噬细胞衰老及衰老相关分泌表型生物活性因子分泌，进而加重脂多糖诱导的肝损伤。

Objective ·To investigate the effects and molecular mechanisms of phosphatidylethanolamine (PE) on macrophage senescence and its senescence-associated secretory phenotype (SASP), as well as its pathophysiological role in liver injury. Methods ·A macrophage senescence model was established using doxorubicin (DOX), followed by PE treatment. A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide (LPS) to investigate the effects of PE on liver injury. Senescence markers and SASP factors, including senescence-associated β-galactosidase (SA-β-gal), cell cycle inhibitor p21, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were evaluated using SA-β-gal staining, quantitative real-time PCR, and Western blotting. RNA sequencing (RNA-seq) was performed, followed by Gene Ontology (GO) cellular component enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis (GSEA), to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence. The expression of endoplasmic reticulum (ER) stress-related proteins, including inositol-requiring enzyme 1 α (IRE1α), spliced X-box binding protein 1 (XBP1s), activating transcription factor 6 (ATF6), ATF4, and C/EBP homologous protein (CHOP), was analyzed through in vivo and in vitro experiments. Results ·PE significantly promoted the expression of senescence markers SA-β-gal, p21, p16 and SASP factors. RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP. Further experiments demonstrated that PE activated the ER stress signaling pathway, promoting macrophage senescence and the expression of SASP factors. In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress. Conclusion ·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway, thereby aggravating LPS-induced liver injury.