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6-5-第五节 小 结
血管内皮细胞在风湿病的发病过程中有重要的作用。各种致病因子,如前炎性细胞因子、自身抗体、炎症细胞等均可通过直接或间接途径作用于内皮细胞,引起内皮细胞损伤或细胞表型改变。同时,内皮细胞也通过自身激活表达多种粘附分子,释放大量炎症细胞因子和血管活性物质,介导炎症细胞的粘附、活化及迁移,并且使血管内皮系统从抗凝状态转变为促凝状态,最终导致炎症细胞在局部的浸润或血管内血栓形成,构成许多血管相关免疫性疾病的病理基础。 0 T i+ N5 M# v& P
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目前在对血管内皮细胞的实验研究中尚存在一些问题。大多数对内皮细胞的体外实验均采用人脐静脉内皮细胞(HUVEC)作为研究对象。有资料表明,人脐静脉和脐动脉的内皮细胞在炎性细胞因子 IL-1, TNF、脂多糖等的刺激下,在 ICAM-1, VCAM-1的表达方面具有差别,TNF可以诱导这两种细胞均表达 ICAM-1,IL-1可以导致这两种细胞均表达VCAM-1,但TNF和 LPS处理后只导致 HUVEC表达VCAM-1。这提示动脉和静脉内皮细胞在炎性因子刺激下表达的粘附分子是有所不同的,并且可能会导致不同疾病的病变血管不同。在用免疫细胞化学方法对人体内的不同血管进行研究后发现,毛细血管的内皮细胞表达大量的主要组织相容性复合物(majorhistocompatibility complex, MHC) I和II、ICAM、 OKM5(单核细胞/内皮细胞标志),而大血管内皮表达大量的vW F和E-选择素,很少或几乎不表达MHC-I和II ,ICAM,OKM5。在对APS和SLE患者的研究中发现,来自相同组患者的血清抗体在HUVEC和人微血管内皮细胞 (human microvascular endothelial cell, HMEC)膜上的结合位点和结合率均有差异。因此不同来源的血管内皮细胞可能具有不同的表型,这可能会导致实验结果的不一致。另外,也需进一步研究反映内皮激活或损伤的指标及其检测方法,虽然目前已有检测可溶性粘附分子、可溶性血栓调理蛋白、vWF等的方法,但各个实验室取得的结果并不一致;并且它们在炎症反应中的作用及分布的细胞各有侧重并互相重叠,在反映内皮激活中的意义尚有待于进一步明确。最近,研究发现在SLE活动期患者的血清中,有表达活化表型的循环内皮细胞(circulating endothelial cell, CEC)数目的升高,并且与血浆 C3a的水平相关。提示它可能反映补体介导的内皮细胞损伤程度。但目前该循环内皮细胞的来源尚不清楚,在内皮激活或损伤中的意义有待于进一步实验来验证。* k Z7 ^& U* `& }2 }
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