皮肤损害过程中肉芽组织形成与微血管结构的关系

Relationship between the formation of granulation tissue and structure of microvessel in the process of cutaneous lesions

目的:皮肤创伤处理不当可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。探讨微血管密度及其基底膜相关成分缺乏机制与PEH病变形成的关系。方法:将11例来自创(烧)伤后继发PEH病变(n=11)及其边缘正常皮肤(PEH-N,n=6)标本,采用免疫组织化学双染色方法观察微血管内皮细胞(micovascularordothelialcell,MEC)CD34、层粘连蛋白(LN)、Ⅳ型胶原、基质金属蛋白酶-2(MMP-2),MMP-3和MMP-9蛋白的表达水平和特征,并结合组织病理学和透射电镜观察MEC组织形态学改变。结果:与PEH-N相比,PEH组织中CD34,LN和Ⅳ型胶原阳性微血管分布密集,但浅层组织MEC的MMP-2,-3,-9蛋白水平升高,尤以MMP-9升高明显,且基底膜LN和Ⅳ型胶原信号显著减弱甚至消失,血管外炎症细胞密集浸润。超微结构显示,浅层肉芽组织中MEC分裂旺盛,缺乏完整的基底膜结构。结论:MEC过度表达MMPs是导致基底膜和间质相关成分缺失、炎症细胞浸润和上皮组织假性瘤样增生等连锁反应的重要环节。

AIM: Inappropriate treatment of skin wounds can induce the formation of pseudo epitheliomatous hyperplasia (PEH) characterized with over proliferation of epithelium and granulation tissue deposition. The aim of this study was to explore the relationship between the formation of PEH and the shortage of microvessel density and the basement membrane components. METHODS:Eleven specimens from PEH and 6 from surrounding normal areas (PEH N) were used for the study.Immunohistochemical double staining was carried out to observe the expression level and characteristics of CD34,laminin (LN),type Ⅳ collagen, matrix metalloproteinase (MMP) 2, MMP 3 and MMP 9 proteins in microwascular endothelial cells (MEC). Histopathology and transmission electron microscope were employed to detect the changes of histomorphology. RESULTS:Compared with PEH N, the CD34, LN and type Ⅳ collagen positive capillaries were intensive, but the protein levels of MMP 2,MMP 3 and MMP 9 were elevated in upper dermis in PEH lesion, especially the MMP 9. However,the positive signals of LN and type Ⅳ collagens in basement membrane decreased dramatically or even disappeared, which was accompanied with the infiltration of inflammatory cells in PEH tissues. The ultrastructure showed that the MEC division increased in granulation tissues, which was deficient of intact basement membrane. CONCLUSION:Over expression of MMPs is the main reason leading to the decrease or depletion of cellular matrix and basement membrane components, and plays an important role in over proliferation of microvessels, infiltration of inflammatary cells and the formation of granulation tissues.