急性放射性皮肤溃疡发生发展过程中多种生长因子及其受体表达水平和对溃疡愈合影响的研究

Expression of several growth factors and their receptors during the formation and development of acute radiation-induced skin ulcers and their effects on ulcer healing:an experimental study

目的 :研究多种生长因子及其受体在急性放射性皮肤溃疡组织中的表达及对溃疡形成和发展的影响。方法 :采用雌性Wistar大鼠 ,以手术法建立单纯皮肤伤口动物模型 ,以60 Coγ射线局部照射法建立急性放射性皮肤溃疡动物模型。观察病变 5 5d ,采用免疫组化、原位杂交和图像分析等方法检测单纯伤口及皮肤溃疡组织中表皮生长因子 (EGF) ,碱性成纤维细胞生长因子 (bFGF) ,血管内皮生长因子 (VEGF) ,血小板衍生生长因子_B(PDGF_B) ,转化生长因子_β1(TGF_β1)等及其受体的转录和表达水平。结果 :照后 14d照射野内开始出现皮肤溃疡 ,之后逐渐扩大、融合、加深。皮肤受照射区多种细胞 ,特别是溃疡床表皮细胞、成纤维细胞及血管内皮细胞中EGF ,bFGF ,PDGF_B ,VEGF等因子及其受体的转录及表达水平均较正常皮肤组织有所增强 ,但与单纯伤口组比较 ,溃疡组织上述因子及其受体的转录及表达水平明显降低。TGF_β1及TGF_βR1在受照射皮肤中表达增强 ,溃疡床的阳性细胞数量较单纯伤口中减少 ,强度未见减弱。结论 :急性放射性皮肤溃疡组织中多种生长因子及其受体表达水平降低可能与放射性皮肤溃疡发生、发展及难愈合 (不能形成有效肉芽组织 )

Objective: To study the expression of several growth factors and their receptors during the formation and development of acute radiation_induced skin ulcers, and their effects on ulcer healing.Methods:Female Wistar rats were used, and a model of simple skin wounds was made. Another rat model which was locally irradiated with 60 Co γ_rays was used, and the pathological changes were observed for 55 days. Immunohistochemistry, in situ hybridization and image analysis were performed to examine EGF, bFGF, VEGF, PDGF_B, TGF_β1 and their receptors in the tissue of radiation skin ulcers. Results: Skin ulcers were found on day 14 after irradiation, and they enlarged and deepened gradually during the observation period. In the irradiated skin, especially in the epidermal cells, fibroblasts and vascular endothelial cells of the ulcer beds,the expression of EGF, bFGF, VEGF, PDGF_B, TGF_β1 and their receptors was higher than that in normal skin,but their expression was suppressed in the ulcer beds as compared with that in the surgical wound beds. The expression of TGF_β1 and TGF_βR1 was elevated in the irradiated skin and was not inhibited in the cells of radiation ulcer beds as compared with that in the simple wound beds. Conclusion: After irradiation, the decreased expression of some growth factors and their receptors in the local skin tissue may play an important role in the formation, development and nonhealing mechanism of radiation skin ulcers.