Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Sci Rep. 2019 Jul 18;9(1):10405. doi: 10.1038/s41598-019-46797-2.
It has been suggested that many forms of secondary lymphedema in humans are driven by a progressive loss of lymphatic pump function after an initial risk-inducing event. However, the link between pump failure and disease progression has remained elusive due to experimental challenges in the clinical setting and a lack of adequate animal models. Using a novel surgical model of lymphatic injury, we track the adaptation and functional decline of the lymphatic network in response to surgery. This model mimics the histological hallmarks of the typical mouse tail lymphedema model while leaving an intact collecting vessel for analysis of functional changes during disease progression. Lymphatic function in the intact collecting vessel negatively correlated with swelling, while a loss of pumping pressure generation remained even after resolution of swelling. By using this model to study the role of obesity in lymphedema development, we show that obesity exacerbates acquired lymphatic pump failure following lymphatic injury, suggesting one mechanism through which obesity may worsen lymphedema. This lymphatic injury model will allow for future studies investigating the molecular mechanisms leading to lymphedema development.
有人提出，人类许多形式的继发性淋巴水肿是由于初始风险诱导事件后淋巴管泵功能的逐渐丧失引起的。然而，由于临床环境中的实验挑战以及缺乏足够的动物模型，泵衰竭与疾病进展之间的联系仍然难以捉摸。我们使用一种新的淋巴损伤手术模型来跟踪淋巴管网络对手术的适应和功能下降。该模型模拟了典型的小鼠尾部淋巴水肿模型的组织学特征，同时保留了一个完整的收集管，用于分析疾病进展过程中的功能变化。完整收集管中的淋巴功能与肿胀呈负相关，而即使肿胀消退后，泵送压力的丧失仍然存在。通过使用该模型研究肥胖在淋巴水肿发展中的作用，我们表明肥胖会加剧淋巴损伤后获得性淋巴泵衰竭，这表明肥胖可能使淋巴水肿恶化的一种机制。这种淋巴损伤模型将允许未来研究导致淋巴水肿发展的分子机制。
