远端肢体缺血调节通过细胞外囊泡介导的肌肝串扰减轻脂肪性肝炎，这一成果由上海交通大学卜军课题组经过不懈努力而取得。这一研究成果发表在2025年3月20日出版的国际学术期刊《细胞—代谢》上。

研究人员报道，远端肢体缺血调节（RIC）是一种临床验证的通过短暂性肌肉缺血来保护远端器官的治疗方法，在不同的motheme模型中显著减轻了脂肪性肝炎。肢体缺血调节的有益作用是通过细胞外小泡（sEVs）及其载货microrna向肝脏的转移介导的，从而导致肝脏中miR-181d-5p的升高。肝脏miR-181d-5p过表达通过抑制核受体4A3 （NR4A3）忠实地反映了肢体缺血适应的分子和组织学益处。

此外，来自肢体缺血状态的人类志愿者的循环sEVs改善了原代人肝细胞和动物模型中的脂肪性肝炎和转录组紊乱。他们的数据强调了肢体缺血调节对脂肪性肝炎治疗的转化潜力，并扩展了他们对心肌-肝脏串音的理解。

据了解，代谢功能障碍相关脂肪性肝炎（MASH）是一种具有不良结局的晚期肝脏疾病。操纵器官间通讯被认为是治疗代谢性疾病（包括脂肪性肝炎）的一种有前途的策略。

附：英文原文

Title: Remote limb ischemic conditioning alleviates steatohepatitis via extracellular vesicle-mediated muscle-liver crosstalk

Author: Yichao Zhao, Ling Gao, Jianqing Chen, Jingze Wei, Guanqiao Lin, Kewei Hu, Wubin Zhao, Weijun Wei, Wei Huang, Lingchen Gao, Ancai Yuan, Kun Qian, Alex F. Chen, Jun Pu

Issue&Volume: 2025-03-20

Abstract: Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of liver disease with adverse outcomes. Manipulating interorgan communication is considered a promising strategy for managing metabolic disease, including steatohepatitis. Here, we report that remote limb ischemic conditioning (RIC), a clinically validated therapy for distant organ protection by transient muscle ischemia, significantly alleviated steatohepatitis in different mouse models. The beneficial effect of limb ischemic conditioning was mediated by muscle-to-liver transfer of small extracellular vesicles (sEVs) and their cargo microRNAs, leading to elevation of miR-181d-5p in the liver. Hepatic miR-181d-5p overexpression faithfully mirrored the molecular and histological benefits of limb ischemic conditioning by suppressing nuclear receptor 4A3 (NR4A3). Furthermore, circulating EVs from human volunteers undergoing limb ischemic conditioning improved steatohepatitis and transcriptomic perturbations in primary human hepatocytes and animal models. Our data underscore the translational potential of limb ischemic conditioning for steatohepatitis management and extend our understanding of muscle-liver crosstalk.

DOI: 10.1016/j.cmet.2025.02.009

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00067-1