淋巴水肿皮肤组织中肥大细胞及其释放的蛋白酶和转化生长因子-β1之间的相关病理研究

Pathological study on mast cells and their released protease and transforming growth factor-β1 in lymphedema skin tissue

目的探讨继发性下肢淋巴水肿患者皮肤组织中肥大细胞分泌的类糜蛋白酶与激活型转化生长因子-β1之间的相互关系,明确淋巴水肿皮肤纤维化的发生发展机制。方法上海交通大学医学院附属第九人民医院整形外科收治7例继发性下肢淋巴水肿患者,均为女性,年龄42~59岁,切取患者患肢皮肤作为实验组;另选7位行面部瘢痕切除术的志愿者,年龄39~54岁,切取下肢正常皮肤组织作为对照组。所有组织标本行Masson染色、类糜蛋白酶和和转化生长因子-β1等抗体的免疫组化和免疫荧光染色以及酶联免疫吸附实验。结果淋巴水肿患者下肢皮肤组织发生了明显的纤维化变性,并且在纤维化的皮肤组织中肥大细胞的数量、类糜蛋白酶的表达、潜在结合肽转化生长因子-β1及转化生长因子-β1的表达均显著高于正常皮肤组织。同时,TGF-β1高表达的淋巴管部位含类糜蛋白酶的肥大细胞也有大量聚集。结论继发性下肢淋巴水肿皮肤组织中类糜蛋白酶和转化生长因子-β1的表达显著增高。类糜蛋白酶的增多可能激活更多的转化生长因子-β1,增多的转化生长因子-β1能促进淋巴水肿皮肤发生纤维化病理改变。

Objective To explore the relationship between protease-chymase secreted by mast cells, and activated transforming growth factor-β1(TGF-β1), in skin with secondary lymphedema(SLE)in lower extremity, so as toidentify the key factors in fibrosis of lymphedema. Methods In this study, the affected limb skin of 7 SLE patients was includedas the experimental group, and normal skin tissue of the lower limb of 7 volunteers was used as controls. The skin samples were assayed by Masson staining, and the expressions of chymase and TGF-β1 were assayed by immunohistochemistry, immunofluorescent staining and enzyme-linked immunosorbent assay. Results There was obvious fibrosis in the skin of lower extremity in patients with lymphedema. The number of MCs andthe expressions of chymase, latency-associated peptide TGF-β1 (LAP TGF-β1) and TGF-β1 were all significantly increased in fibrotic skin in lymphedema, compared with those in normal skin. At the same time, the chymase-containing mast cells accumulated in the lymphatic vessels, with higher expression of TGF-β1. Conclusions The expression of chymase and TGF-β1 was significantly increased in the fibrotic skin insecondary lower extremity lymphedema. The increased expression of chymase in the skin may activate more TGF-β1 expression, and the increased TGF-β1 may promote skin fibrosis in SLE.