Dong Dong, Wang Heng, Chen Liang, Wang Wei, Liu Tianyi
Department of Plastic and Aesthetic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Shanghai Medical College of Fudan University, Shanghai, China.
Front Pharmacol. 2022 Mar 31;13:853859. doi: 10.3389/fphar.2022.853859. eCollection 2022.
Transplantation of lymph nodes (LNs) is an increasingly popular option for treating lymphedema. Increasing evidence indicates an intrinsic correlation between estrogen signaling and the lymphatic system. We explored the effects of 17β estradiol and antiestrogen treatment (tamoxifen) on the survival and functional restoration of transplanted popliteal lymph nodes (PLNs). A total of forty-eight ovariectomized mice were divided into three groups of 16: OVX + E2 (treated with 17β-estradiol), OVX + TMX (treated with tamoxifen), and OVX (control; treated with olive oil as a solvent). After 2 weeks, PLNs were transplanted. Then, reconnections of lymphatic vessels were observed, and the morphology and survival of transplanted PLNs were evaluated 4 weeks after transplantation. T cells, B cells, lymphatic vessels, and high endothelial venules (HEVs) were subjected to immunofluorescence staining or immunohistochemical staining and quantified. The percentage of lymphatic reconnections was 93.75% in the OVX + E2 group, 68.75% in the OVX + TMX group, and 75% in the OVX group. Surviving PLNs were observed in 16 of 16 in the OVX + E2 group, seven of 16 in the OVX + TMX group, and 13 of 16 in the OVX group. The mean size of PLNs in the largest cross section of the OVX + TMX group was significantly lower than that in the other groups. The distributions of B cells and T cells in surviving PLNs were similar to those in normal LNs. The ratio of dilated HEVs/total HEVs and density of lymphatic vessels in the OVX + E2 group were the highest among the three groups, whereas the lowest ratio and density were observed in the OVX + TMX group. Tamoxifen treatment might lead to cellular loss of transplanted LNs and interfere with the structural reconstruction and functional restoration, thereby inhibiting the survival of transplanted PLNs. Estrogen treatment facilitated the maintenance and regeneration of functional HEVs as well as lymphangiogenesis.
淋巴结移植是治疗淋巴水肿越来越常用的方法。越来越多的证据表明雌激素信号与淋巴系统之间存在内在关联。我们探讨了17β-雌二醇和抗雌激素治疗（他莫昔芬）对移植的腘窝淋巴结（PLN）存活及功能恢复的影响。将48只去卵巢小鼠分为3组，每组16只：OVX + E2组（用17β-雌二醇治疗）、OVX + TMX组（用他莫昔芬治疗）和OVX组（对照组；用橄榄油作为溶剂治疗）。2周后，移植PLN。然后，观察淋巴管的重新连接情况，并在移植后4周评估移植PLN的形态和存活情况。对T细胞、B细胞、淋巴管和高内皮微静脉（HEV）进行免疫荧光染色或免疫组织化学染色并定量分析。OVX + E2组的淋巴管重新连接百分比为93.75%，OVX + TMX组为68.75%，OVX组为75%。OVX + E2组16只小鼠中有16只观察到存活的PLN，OVX + TMX组16只中有7只，OVX组16只中有13只。OVX + TMX组最大横截面处PLN的平均大小显著低于其他组。存活PLN中B细胞和T细胞的分布与正常淋巴结中的相似。OVX + E2组扩张的HEV/总HEV的比例和淋巴管密度在三组中最高，而OVX + TMX组的比例和密度最低。他莫昔芬治疗可能导致移植淋巴结细胞丢失，并干扰结构重建和功能恢复，从而抑制移植PLN的存活。雌激素治疗促进了功能性HEV的维持和再生以及淋巴管生成。
