An Experimental Study for Mouse Lymphedema Model / 대한혈관외과학회지

ABSTRACT

PURPOSE: Lymphedema is a disease with a poorly understood pathogenesis and without definite ways of treatment, yet it can lead to serious complications. The purpose of this study was to establish a new lymphedema mouse model and to evaluate its usefulness for future studies. METHODS: A lymphedema model was created by interrupting flow from the superficial lymphatic system (skin and subcutaneous tissue removal, electrocautery) and the deep lymphatic system (hindlimb muscle resection, dye injection, and inguinal lymph node dissection). The lymphedema group (n=10) was compared to a control group (n=10) by assessing the differences in hindlimb edema, through the use of a water displacement volumetry method. In addition, lymphoscintigraphy, immunohistochemistry, and reverse transcription- polymerase chain reaction (RT-PCR) were performed and compared between the 2 groups. RESULTS: Volumetric analysis showed that the lymphedema group had a 2-fold increase in swelling compared to the control group at study day 3; this gradually decreased to normal levels after 8 weeks. Staining showed an increase in fibrosis in the lymphedema group, as well as an increase in vascular endothelial growth factor receptor-3, a receptor specific for lymphatic cells. RT-PCR showed that there was increased expression of the lymphatic cell specific markers, Prox-1 and podoplanin, in the distal portion of the hindlimb. Lymphoscintigraphy showed retention of lymphatic flow after 30 minutes, however, eventually all of the radioactive substance drained out from the hindlimb. CONCLUSION: Our method for creation of lymphedema in mice was effective in creating acute lymphedema. However it failed to retain its edematous properties for long periods of time. Further studies are needed to create a novel method of chronic lymphedema.