在老年小鼠中,Sirt1-eIF2α轴通过ER压力加剧肝脏IRI驱动促炎性巨细胞激活
Yun Zhou1, Xinglang Wu1, Xuesong Xu1
1Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 40010, China.
Biochemical and biophysical research communications
|March 3, 2026
概括
用NMN补充老年小鼠对抗缺血-再输血后的肝损伤. NMN恢复了巨细胞的功能,减少了炎症并改善了肝移植的移植活力.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 衰老研究研究 衰老研究
背景情况:
- 老年供体肝脏增加了移植后的缺血-再输液损伤 (IRI).
- 在IRI后的老年肝脏中,肝损伤和促炎性巨细胞两极分化恶化.
- 这与真核细胞翻译启动因子2α (eIF2α) 乙化增加有关.
研究的目的:
- 研究β-尼古丁胺胺 mononucleotide (NMN) 在减轻与年龄相关的肝脏IRI的治疗潜力.
- 探索NAD+代谢和Sirt1活性在IRI后老年肝细胞巨细胞中的作用.
主要方法:
- 使用过的老老鼠接受了肝脏IRI.
- 评估了巨细胞极化,eIF2α乙化,NAD+水平和Sirt1活动.
- 在体内和体外给予NMN以评估其作用.
主要成果:
- 在老年小鼠中,IRI加剧了晚期肝损伤,与增加的eIF2α乙化和促炎性巨细胞两极分化相关.
- NAD+水平下降,降低了Sirt1的活性,并损害了其脱乙酶功能,导致eIF2α过乙化.
- 补充NMN恢复了Sirt1活性,减少了eIF2α乙化,减轻了内分泌网膜应激,并抑制了前炎性细胞因子表达.
结论:
- 通过恢复Sirt1活性和调节巨细胞表型,NMN有效地减轻与年龄相关的肝脏IRI.
- 在老年肝细胞中,NMN可降低内等质网膜应激和前炎性反应.
- 作为一种治疗剂,NMN显示出有前途,可以增强来自老年捐赠者的边缘肝移植的活力.
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