近日，南开大学陈瑶团队报道了一种可扩展的基于COF的隔离剂用于脂肪肝的协同胆汁酸调节。相关论文发表在2026年3月11日出版的《美国化学会志》上。

代谢功能障碍相关脂肪肝病（MAFLD）与胆固醇代谢异常及胆汁酸失衡密切相关，已成为快速增长的临床挑战。

研究组提出一种协同阴离子交换/孔道吸附策略，利用高稳定性且具备生物/工业兼容性的烯烃连接共价有机框架平台作为口服胆汁酸吸附剂，用于治疗MAFLD。该协同机制使COFs能高效选择性吸附去质子化和质子化两种形态的胆汁酸，同时避免营养物质吸附。通过体外和体内实验验证，其吸附性能显著优于仅靶向去质子化胆汁酸且易导致营养流失的临床药物消胆胺。

值得注意的是，在高脂饮食诱导的MAFLD小鼠模型中，为期10周的COF治疗显著降低血清总胆固醇、低密度脂蛋白胆固醇水平及肝损伤标志物，从而减轻肝脂肪变性、炎症反应和整体肝损伤。该研究不仅确立了COFs作为下一代口服吸附剂的潜力，更为通过分子工程材料靶向代谢性疾病提供了机制性蓝图。

附：英文原文

Title: A Scalable COF-Based Sequestrant for Synergistic Bile Acid Modulation in Fatty Liver Disease

Author: Jian Wang, Chaonan Jin, Sa Wang, Yingxiao Sun, Ting Wang, Xiaotong Yu, Jinxia Wei, Zhenjie Zhang, Yubo Li, Yao Chen

Issue&Volume: March 11, 2026

Abstract: Metabolic dysfunction-associated fatty liver disease (MAFLD), closely linked to abnormal cholesterol metabolism and bile acid imbalance, has become a rapidly increasing clinical challenge. Herein, we develop a synergistic anion-exchange/pore-adsorption strategy for treating MAFLD using a highly stable, bio/industrial-compatible olefin-linked covalent organic framework (COF) platform as an oral bile acid (BA) adsorbent. This synergistic approach enables the COFs to efficiently and selectively adsorb both deprotonated and protonated BAs while avoiding nutrient adsorption. The adsorbent performance significantly surpasses that of the clinical drug cholestyramine, which targets only deprotonated BAs and often leads to nutrient loss, as validated by in vitro and in vivo experiments. Notably, in a high-fat-diet-induced MAFLD mouse model, a 10-week COF treatment markedly reduced serum levels of total cholesterol and low-density lipoprotein cholesterol as well as liver injury markers, thereby alleviating hepatic steatosis, inflammation, and overall liver damage. This study not only establishes COFs as a promising class of next-generation oral adsorbents but also offers a mechanistic blueprint for targeting metabolic disorders through molecularly engineered materials.

DOI: 10.1021/jacs.5c17573

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c17573