Quantification of Chronic Lymphedema in a Revised Mouse Model
Quantification of Chronic Lymphedema in a Revised Mouse Model
复制标题
DOI：
10.1097/sap.0000000000001537
复制
发表时间：
2018-11-01
影响因子：
1.5
通讯作者：
Sorensen, Jens Ahm
中科院分区：
文献类型：
--
作者：
Jorgensen, Mads Gustaf;Toyserkani, Navid Mohammadpour;Sorensen, Jens Ahm
背景 淋巴水肿是通过手术淋巴结切除和放射治疗进行癌症治疗后的一种常见且使人衰弱的并发症。目前尚无针对淋巴水肿的治愈方法。旨在复制这种疾病的动物模型还不够充分，导致从实验治疗研究到临床的过渡遇到了麻烦。因此，建立能够可靠地复制临床淋巴水肿的实验动物模型势在必行。方法为了寻找诱导淋巴水肿的最佳方法，在8个实验组（n = 4）中将手术淋巴消融和放射或硅胶夹板放置相结合。总共有 32 只小鼠参与了这项研究，并在手术后随访了 8 周。结果包括显微计算机断层扫描后肢体积测定、用锝 Tc 99m (Tc-99m) 人血清白蛋白淋巴闪烁扫描法测量的淋巴清除率以及用 LYVE-1 免疫组织化学定量的淋巴管扩张。 结果 所有试验模型除一种外仅导致短暂性淋巴水肿或具有不良发病率的持续性淋巴水肿。淋巴阻塞手术与 2 次 10 Gy 照射相结合，成功诱导了持久的淋巴水肿，且无不良事件。在8周的随访中，与未手术的肢体相比，所有时间点的肢体体积均显着增加（P < 0.001），淋巴引流受损（P < 0.001），淋巴管扩张（P < 0.001）。结论所提出的获得性淋巴水肿模型是对先前工作的简化和改进，可以移植到未来的观察性和介入性研究中。此外，还展示了 Tc-99m-HSA 淋巴闪烁显像如何量化淋巴清除率，这可以在旨在增强淋巴引流的治疗研究中提供深刻的见解。
Background Lymphedema is a common and debilitating complication following cancer treatment with surgical lymph node excision and radiotherapy. Currently there are no curative treatments for lymphedema. Animal models that intended to replicate the disease have been inadequate, making a troublesome transition from experimental therapeutic studies into the clinic. It is therefore imperative to establish an experimental animal model that can reliably replicate clinical lymphedema.Methods To discover the optimal method of lymphedema induction, surgical lymph ablation and irradiation or silicone splint emplacement were combined in 8 experimental groups (n = 4). In total, 32 mice served in this study and were followed for 8 weeks after surgery. Outcomes included micro-computed tomography hind limb volumetry, lymphatic clearance measured with technetium Tc 99m (Tc-99m) human serum albumin lymphoscintigraphy and lymph vessel ectasia quantified with LYVE-1 immunohistochemistry.Results All trialed models but one resulted in only transient lymphedema or lasting lymphedema with adverse morbidity. Combined surgical lymph obstruction with 2 fractions of 10-Gy irradiation successfully induced lasting lymphedema without adverse events. Over the 8 weeks' follow-up, limb volumes were significantly increased at all time points (P < 0.001), lymph drainage was impaired (P < 0.001), and lymph vessels were ectatic (P < 0.001), when compared with the unoperated limbs.Conclusions The presented model of acquired lymphedema is a reduction and refinement of previous works and can transpose to future observational and interventional studies. In addition, it is shown how Tc-99m-HSA lymphoscintigraphy can quantify lymphatic clearance, which can prove insightful in therapeutic studies aiming to enhance lymphatic drainage.