A refined mouse hind limb model of secondary lymphedema

作者:Dai, Tingting; Cui, Chunxiao; Cao, Weigang*; Jiang, Zhaohua*; Li, Shengli*
来源:International Journal of Clinical and Experimental Medicine, 2016, 9(4): 7565-7572.

摘要

Background: This study aimed at establishing a more stable and persistent mouse lymphedema model through modification of radiation dose and administrating timing. Methods: Mice lymphedema models were created by using a combination of lymph node removal and radiation treatment. The experiment groups received the following treatments at varied time points: "surgery before radiation" group (S+R group; n = 12), 4.5 Gy at 2 weeks after surgical treatment; "radiation treatment before surgery" group (R+S group; n = 12), 4.5 Gy at 3 days before surgery; and "radiation before and after surgery" group (r+S+r group; n = 12), 2.25 Gy at both 3 days before and 2 weeks after surgery. Volume change was compared by using the water replacement method. Lymphatic vessel distribution was visualized by in vivo lymphatic imaging with fluorescence nanogel. Immunohistochemistry staining was performed to show superficial lymphatic vessels. Lymphatic vessel density was compared. Results: All the treated mice developed hind limb lymphedema. The r+S+r group showed the most stable hind limb lymphedema during our observation period of 6 months, with lower mortality and morbidity rates. At 6 months post operation, lymphatic imaging revealed superficial lymphatic network for all the groups. The number of lymphatic vessels passing through the surgical scar was significantly higher (P < 0.05) in the R+S (n = 9) and S+R groups (n = 9) than in the r+S+r group (n = 10). Immunohistochemistry revealed a significantly higher number of lymphatic vessels distal to the treated area in the r+S+r group than in control and R+S groups (P < 0.05). Conclusion: A radiation dose of 2.25 Gy administered 3 days before surgery and 2 weeks after surgery successfully enhanced the stability of the mice hind limb lymphedema model.