新加坡国立大学Veronique Angeli小组近日取得一项新成果。经过不懈努力，他们的研究认为靶向过度胆固醇沉积可减轻继发性淋巴水肿。相关论文于2026年2月11日发表在《自然》杂志上。

在这里，课题组人员显示淋巴引流不足在人类淋巴水肿导致过多的胆固醇积聚在淋巴水肿真皮组织和淋巴管周围。胆固醇沉积导致真皮脂肪组织重塑，以脂肪细胞肥大和功能障碍为特征，进展到死亡和真皮纤维化。手术干预改善淋巴引流，减少胆固醇沉积。通过使用两种重现人类淋巴水肿特征的小鼠模型，该团队证明了消耗胆固醇的环糊精可以改善组织肿胀和真皮脂肪组织重塑。在机制上，该研究团队证明了环糊精通过促进淋巴管再生来恢复淋巴引流。本研究揭示了胆固醇清除受损在驱动淋巴水肿中的作用，并确定组织胆固醇是这种目前无法治愈的疾病的有希望的治疗靶点。

据了解，淋巴水肿是一种慢性衰弱性疾病，由淋巴引流受损引起，其特征是组织肿胀、脂肪扩张、炎症和纤维化。然而，导致淋巴水肿的确切机制尚不清楚。虽然已知淋巴管可将胆固醇从外周组织转运回体循环，但淋巴引流受损对人体胆固醇清除的重要性及其与淋巴水肿的相关性尚不清楚。

附：英文原文

Title: Targeting excessive cholesterol deposition alleviates secondary lymphoedema

Author: Lim, Hwee Ying, Zhang, Yuning, Azhar, Syaza Hazwany Mohammad, Thiam, Chung Hwee, Taylor, Michaela, Koh, Xuan Han, Yunos, Mohamed Ameen Shah Bin Mohamed, Tan, Shu Wen, Lim, Sheau Yng, Ong, Wei Siong, Goh, Jasmine, Ng, Si Hui, Cochran, Blake J., Tham, Wai Kin, Ang, Owen, Lim, Sheng Jie, Lim, Tze Chin, Chen, Yanjun, Mause, Sebastian Frederik, Torta, Federico, Wenk, Markus R., Rye, Kerry-Anne, Tan, Bien Keem, Angeli, Veronique

Issue&Volume: 2026-02-11

Abstract: Lymphoedema is a chronic debilitating disease caused by impaired lymphatic drainage and is characterized by tissue swelling, fat expansion, inflammation and fibrosis1,2. However, the exact mechanisms that drive lymphoedema are poorly understood. Although lymphatic vessels are known to transport cholesterol from peripheral tissues back to the systemic circulation3, the importance of impaired lymphatic drainage for cholesterol clearance in humans and its relevance to lymphoedema remain unknown. Here we show that lymphatic drainage insufficiency in human lymphoedema leads to excessive cholesterol accumulation in the lymphoedematous dermal tissue and around lymphatic vessels. Cholesterol deposition resulted in dermal adipose tissue remodelling, characterized by adipocyte hypertrophy and dysfunction, progressing to death and dermal fibrosis. Surgical intervention improved lymphatic drainage and reduced cholesterol deposition. Using two mouse models that reproduce features of human lymphoedema, we demonstrated that tissue swelling and dermal adipose tissue remodelling were ameliorated by the cholesterol-depleting agent cyclodextrin. Mechanistically, we demonstrated that cyclodextrin restored lymphatic drainage by promoting the regeneration of lymphatic vessels. This study unravels the role of impaired cholesterol clearance in driving lymphoedema and identifies tissue cholesterol as a promising therapeutic target for this currently incurable disease.

DOI: 10.1038/s41586-025-10016-y

Source:https://www.nature.com/articles/s41586-025-10016-y