基线淋巴功能障碍加剧了淋巴损伤的负面影响。
Baseline Lymphatic Dysfunction Amplifies the Negative Effects of Lymphatic Injury.
机构信息
From the Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center.
出版信息
Plast Reconstr Surg. 2019 Jan;143(1):77e-87e. doi: 10.1097/PRS.0000000000005091.
BACKGROUND
Genetic mutations and obesity increase the risk of secondary lymphedema, suggesting that impaired lymphatic function before surgical injury may contribute to disease pathophysiology. Previous studies show that obesity not only decreases lymphatic function, but also markedly increases pathologic changes, such as swelling, fibroadipose deposition, and inflammation. However, although these reports provide circumstantial evidence supporting the hypothesis that baseline lymphatic defects amplify the effect of lymphatic injury, the mechanisms regulating this association remain unknown.
METHODS
Baseline lymphatic morphology, leakiness, pumping, immune cell trafficking, and local inflammation and fibroadipose deposition were assessed in wild-type and Prox1-haploinsufficient (Prox1) mice, which have previously been shown to have abnormal vasculature without overt evidence of lymphedema. In subsequent experiments, wild-type and Prox1 mice underwent popliteal lymph node dissection to evaluate the effect of lymphatic injury. Repeated testing of all variables was conducted 4 weeks postoperatively.
RESULTS
At baseline, Prox1 mice had dilated, leaky lymphatic vessels corresponding to low-grade inflammation and decreased pumping and transport function, compared with wild-type mice. Popliteal lymph node dissection resulted in evidence of lymphedema in both Prox1 and wild-type mice, but popliteal lymph node dissection-treated Prox1 mice had increased inflammation and decreased lymphatic pumping.
CONCLUSIONS
Subclinical lymphatic dysfunction exacerbates the pathologic changes of lymphatic injury, an effect that is multifactorial and related to increased lymphatic leakiness, perilymphatic accumulation of inflammatory cells, and impaired pumping and transport capacity. These findings suggest that preoperative testing of lymphatic function may enable clinicians to more accurately risk-stratify patients and design targeted preventative strategies.
背景
遗传突变和肥胖会增加继发性淋巴水肿的风险，这表明手术损伤前的淋巴功能障碍可能导致疾病的病理生理学改变。先前的研究表明，肥胖不仅会降低淋巴功能，还会显著增加病理变化，如肿胀、纤维脂肪沉积和炎症。然而，尽管这些报告提供了支持这样一种假设的间接证据，即基线淋巴缺陷会放大淋巴损伤的效应，但调节这种关联的机制仍不清楚。
方法
在野生型和 Prox1 杂合不足（Prox1）小鼠中评估了基线淋巴形态、渗漏性、泵送、免疫细胞迁移以及局部炎症、纤维脂肪沉积，此前的研究表明这些小鼠存在异常的脉管系统，但没有明显的淋巴水肿证据。在随后的实验中，野生型和 Prox1 小鼠接受了隐鼠淋巴结解剖，以评估淋巴损伤的影响。术后 4 周重复所有变量的测试。
结果
在基线时，与野生型小鼠相比，Prox1 小鼠的淋巴血管扩张、渗漏，对应于低度炎症和降低的泵送和转运功能。隐鼠淋巴结解剖导致 Prox1 和野生型小鼠均出现淋巴水肿的证据，但隐鼠淋巴结解剖处理后的 Prox1 小鼠炎症增加，淋巴泵送功能降低。
结论
亚临床淋巴功能障碍加剧了淋巴损伤的病理变化，这种效应是多因素的，与淋巴通透性增加、周围淋巴积聚炎症细胞以及泵送和转运能力受损有关。这些发现表明，术前淋巴功能测试可以使临床医生更准确地对患者进行风险分层，并设计有针对性的预防策略。
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