近日，美国寺崎生物医学创新研究所研究团队的研究报道了迷走神经阻断脑-肝轴阻止癌症相关恶病质。这一研究成果于2025年8月7日发表在国际顶尖学术期刊《细胞》上。
在这项研究中，研究人员发现癌症诱导的全身性炎症改变了CAC母细胞模型的迷走神经张力。这种迷走神经失调破坏了脑-肝迷走神经轴，通过耗尽HNF4α（肝功能的关键转录调节因子）导致肝脏蛋白质代谢的重编程。HNF4α的缺失破坏肝脏代谢，促进全身性炎症，导致恶病质表型。通过手术、化学、电或非侵入性经皮装置对右颈迷走神经进行干预，可减弱CAC的进展，减轻其临床表现，并与化疗协同作用，改善小鼠的整体健康状况和生存率。
据介绍，癌症相关恶病质（CAC）是一种多因素且目前无法治愈的综合征，导致近三分之一的癌症相关死亡。它有助于抵抗治疗并增加受影响患者的死亡率。
附：英文原文
Title: Vagal blockade of the brain-liver axis deters cancer-associated cachexia
Author: Aliesha Garrett, Naama Darzi, Ashlesha Deshmukh, Nataly Rosenfeld, Omer Goldman, Lital Adler, Elizabeta Bab-Dinitz, Oded Singer, Alireza Hassani Najafabadi, Chi Wut Wong, Shree Bose, Peggy M. Randon, Francisco Bustamante, Rene Larios, Alexander Brandis, Tevie Mehlman, Brandon Smaglo, Ping Chang, Jacqueline Oliva, Cara Haymaker, Laukik Nagawekar, Sophie R. Wu, Yixuan Huang, Aidan Shen, Ahana Vora, Jon Floyd Padilla, Alissa Pfeffer, Gary Sutherland, Mark Starr, Teresa Zimmers, Yangzhi Zhu, James Morizio, Ayelet Erez, Xiling Shen
Issue&Volume: 2025-08-07
Abstract: Cancer-associated cachexia (CAC) is a multifactorial and currently incurable syndrome responsible for nearly one-third of cancer-related deaths. It contributes to therapy resistance and increases mortality among affected patients. In this study, we show that cancer-induced systemic inflammation alters vagal tone in CAC mouse models. This vagal dysregulation disrupts the brain-liver vagal axis, leading to a reprogramming of hepatic protein metabolism through the depletion of HNF4α, a key transcriptional regulator of liver function. The loss of HNF4α disrupts hepatic metabolism and promotes systemic inflammation, resulting in cachectic phenotypes. Interventions targeting the right cervical vagus nerve surgically, chemically, electrically, or through a non-invasive transcutaneous device attenuate CAC progression, alleviate its clinical manifestations, and synergize with chemotherapy to improve overall health and survival in mice.
DOI: 10.1016/j.cell.2025.07.016
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00805-0