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继发性淋巴水肿的小鼠尾部模型:纤维化逐渐加重且不可逆。

Mouse tail models of secondary lymphedema: fibrosis gradually worsens and is irreversible.

作者信息

Zhou Chenxiao, Su Wanchun, Han Haotian, Li Na, Ma Gang, Cui Lei

机构信息

Department of Plastic Surgery, Beijing Shijitan Hospital, Capital Medical University Beijing 100038, China.

Department of Lymph Surgery, Beijing Shijitan Hospital, Capital Medical University Beijing 100038, China.

出版信息

Int J Clin Exp Pathol. 2020 Jan 1;13(1):54-64. eCollection 2020.

PMID:32055273
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7013376/
Abstract

Although the mouse tail model of secondary lymphedema has been widely used in research, our knowledge regarding some of the characteristic changes in this model is lacking. Therefore, in the current study, we aimed to identify pathologic changes after surgery. Tail lymphedema was created in C57BL/6J mice by disconnecting both superficial and deep lymphatic vessels. The surgery resulted in chronic edema formation with the proliferation of subcutaneous adipose tissue, deposition of fibrotic tissue, and gradual increase in CD4 T lymphocyte infiltration. Furthermore, dramatic expansion and an increased number of lymphatic vessels were observed postoperatively. Lymphatic reflux was established at least 8 weeks after surgery, as evidenced by staining of the scar from the surgical excision. In addition, tissue fibrosis was irreversible, although CD4 T cell infiltration, tail swelling, and subcutaneous adipose hyperplasia were alleviated over time. We also show that necrosis could be effectively avoided by paying attention to several details in the modeling process. As animal models play a key role in exploring the pathophysiology of disease, our findings provide strong support for the study of lymphedema. The irreversibility of fibrosis suggests the importance of treating lymphedema by preventing fibrosis development.

摘要

尽管继发性淋巴水肿的小鼠尾部模型已在研究中广泛应用,但我们对该模型中一些特征性变化的了解仍然不足。因此,在本研究中,我们旨在确定手术后的病理变化。通过切断C57BL/6J小鼠的浅、深淋巴管来制造尾部淋巴水肿。手术导致慢性水肿形成,伴有皮下脂肪组织增生、纤维化组织沉积以及CD4 T淋巴细胞浸润逐渐增加。此外,术后观察到淋巴管显著扩张且数量增加。手术切除瘢痕染色证明,术后至少8周建立了淋巴回流。另外,尽管随着时间推移CD4 T细胞浸润、尾部肿胀和皮下脂肪增生有所减轻,但组织纤维化是不可逆的。我们还表明,通过注意建模过程中的几个细节可以有效避免坏死。由于动物模型在探索疾病病理生理学方面起着关键作用,我们的研究结果为淋巴水肿的研究提供了有力支持。纤维化的不可逆性表明通过预防纤维化发展来治疗淋巴水肿的重要性。

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CD4 T cells are activated in regional lymph nodes and migrate to skin to initiate lymphedema.CD4 T 细胞在区域性淋巴结中被激活,并迁移到皮肤以引发淋巴水肿。
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