Histochemical and biochemical modifications induced by experimental irradiation of human skin maintained in survival conditions and modulation by application of an emulsion containing trolamine.

S Boisnic, M C Branchet-Gumila, D Nizri, L Ben Slama
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Abstract

Radiotherapy continues to cause skin disorders. In this article, with the aid of our human skin model maintained in ex vivo survival conditions for 15 days, we describe the modifications caused by irradiation and their modulation by a trolamine-containing emulsion (Biafine). Normal human skin fragments were maintained in organ culture. One ionizing radiation session with 5 Gy was applied. Skin parameters were evaluated 24 h after the radiation session and were compared with a nonirradiated skin fragment: vascular modifications (histology), edema, epithelial proliferation, interleukin (IL)-1alpha and IL-6. Another series of skin fragments was maintained in survival conditions for 15 days after the radiation session to evaluate collagen neosynthesis by fibroblasts and any vascular changes (CD34). After irradiation the basal cell proliferation was reduced by approximately 50%. Extensive vasodilation occurred with altered capillary permeability accompanied by decreased CD34 transmembrane protein expression. Collagen synthesis and IL-1 secretion were increased. Biafine significantly reduced capillary alterations, restored CD34 expression as well as epithelial cell proliferation and significantly decreased collagen synthesis and IL-1 expression. With this ex vivo human skin model we confirmed the main modifications induced by radiotherapy as previously described in animal models: decreased basal cell proliferation and endothelial cell alterations and increased collagen synthesis by fibroblasts, probably under the influence of IL-1. The effect of Biafine emulsion on these histological and biochemical parameters may support its clinical efficacy.

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人体皮肤在生存条件下的实验性照射和含有三胺的乳剂的应用所引起的组织化学和生化变化。
放射治疗继续引起皮肤疾病。在这篇文章中,我们借助在离体生存条件下维持15天的人体皮肤模型,描述了辐射引起的修饰以及含三硝胺的乳剂(Biafine)对其的调节。在器官培养中维持正常人皮肤碎片。应用了一次5戈瑞的电离辐射。照射后24小时评估皮肤参数,并与未照射的皮肤片段进行比较:血管改变(组织学)、水肿、上皮细胞增殖、白细胞介素(IL)-1 α和IL-6。另一组皮肤碎片在放疗后的存活条件下维持15天,以评估成纤维细胞的胶原新合成和任何血管变化(CD34)。照射后基底细胞增殖减少约50%。血管广泛舒张,毛细血管通透性改变,CD34跨膜蛋白表达降低。胶原合成和IL-1分泌增加。Biafine显著降低毛细血管改变,恢复CD34表达和上皮细胞增殖,显著降低胶原合成和IL-1表达。通过这种离体人体皮肤模型,我们证实了先前在动物模型中描述的放疗引起的主要变化:基底细胞增殖和内皮细胞改变减少,成纤维细胞合成胶原增加,可能是在IL-1的影响下。比芬乳剂对这些组织学和生化指标的影响可能支持其临床疗效。
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