假性上皮瘤样增生病变中上皮-间质连接区基底膜相关成分缺失机制的研究

Study of mechanism on loss of some components from basement membrane in epithelialCinterstitial junction in cutaneous pseudoepitheliomatous hyperplasia lesion

目的 探讨上皮间质连接 (EIJ)的基底膜 (BM)成分缺失在皮肤创伤治疗中引发以上皮和肉芽组织过度增生为特征的假性上皮瘤样增生 (PEH)病变的机制。方法 采集 11例临床创 (烧 )伤后继发 PEH病变及 6例其边缘正常皮肤 (PEH N)标本 ,用免疫组织化学方法观察 EIJ区广谱细胞角蛋白 (p CK)、 型胶原 (Col )、层黏连蛋白 (L N)、基质金属蛋白酶 2 (MMP 2 )、MMP 3和 MMP 9、增殖细胞核抗原(PCNA)、上皮钙黏蛋白 (E Cad)和β连接蛋白 (β Cat)的免疫反应性和分布特征 ,并结合组织病理学和透射电镜观察该区域形态学改变。结果 与 PEH N组相比 ,PEH组 p CK阳性表皮呈鳞状上皮化并向深层间质伸展。在 Col 和 L N信号减弱或阴性的 EIJ处 ,表皮基底细胞表达 p CK、E Cad、MMP 2、MMP 3和 MMP 9的水平下降 ,相反 β Cat和 PCNA免疫化学染色明显增强 ,可见基底细胞向间质迁移或脱落 ,并在间质内检测到 p CK阳性上皮岛和游离的上皮细胞。相同部位超微结构显示 ,上皮基底细胞变形、核 /浆比增加 ,细胞间连接减少、间隙增宽 ,BM电子密度降低、结构紊乱或与基底细胞分离。结论 创伤相关的 PEH上皮基底细胞黏附、分化以及对基底膜和角蛋白结构形成能力的下降 ,是其向间质迁移和脱落的重要原因。EIJ的 BM内 Col 和 L

Objective To investigate the relationship between the formation of pseudoepitheliomatous hyperplasia(PEH) and the mechanism of loss of some components from the basement membrane in epithelial interstitial junction(EIJ) in the treatment of cutaneous wounds, when formation of PEH lesion was induced. Methods Morphological change in epithelial tissue was observed with histopathologic method and electronic microscopy in 11 specimens of PEH lesions and 6 specimens of normal skin adjacent to PEH (PEH-N) from 11 patients with injured skin. The expression characteristics and distribution of pan- cytokeratin (p-CK), matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-9, proliferating cell nuclear antigen(PCNA), epithelial cadherin(E-Cad) and β-catenin(β-Cat) in EMJ were detected with immunohistochemical methods. Results Epithelial cells expressing P-CK presented squamous epithelization and extended into deep layer of mesenchyma. In epithelium-mesenchyma junction, where Ⅳ type collagen and laminin were weakly expressed, the protein contents of p-CK, E-Cad, MMP-2, MMP-3 MMP-9 were decreased, whilst the immunochemical staining of βCCat and PCNA was apparently increased. In the junction, epithelial basal cells were observed to migrate and to depart from basal membrane, epithelial islands and isolated epithelial cells expressing p-CK in mesenchyma could be observed. Ultrastructural observation revealed deformation of epithelial basal cells, increment of nucleus/cytoplasm ratio, loosened intercelluar junctions, decrement of electronic density of BM and derangement of BM stucture could be observed. Conclusion Reduction in the capability of epithelial basal cells adhesion, differentiation and formation of basement membrane and cytokeratin in PEH associated with wound may be the crucial cause which controls epithelial cells migration into mesenchyma. That the contents of ColⅣ and LN were decreased may not be associated with MMPs, but with enhancement of the ratio of β-Cat/E-Cad signal might be the important mechanism of dedifferentiation of epithelial basal cells and the loss of ability of structure formation and cellular migration.