急性放射性皮肤溃疡发生发展过程中TGF-β1及其受体TGF-βR1的表达水平:与单纯伤口愈合的定量对比研究

EXPRESSION OF TGF-β1 AND TGF-βR1 DURING THE FORMATION AND DEVELOPMENT OF RADIATION-INDUCED SKIN ULCERS AND THEIR EFFECTS ON ULCER HEALING: A COMPARATIVE STUDY WITH NORMAL WOUND HEALING

为研究TGF-β1及其受体TGF-βR1在急性放射性皮肤溃疡组织中的表达水平及对溃疡形成、发展、愈合的影响,我们采用雌性Wistar大鼠,以60Coγ射线局部照射法建立急性放射性皮肤溃疡动物模型,并以手术法建立单纯皮肤伤口动物模型,观察病变55天,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TGF-β1及TGF-βR1的转录和表达水平。研究发现,照后14天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TGF-β1及TGF-βR1的转录和表达水平均较正常皮肤组织明显增强,与单纯伤口组比较,溃疡床的TGF-β1及TGF-βR1阳性细胞数量明显减少,阳性强度减弱不明显。表明放射性皮肤溃疡组织中TGF-β1及TGF-βR1的表达水平降低可能与溃疡发生、发展及难愈合的分子机制相关。

To study the expression of TGF-β1 and TGF-βR1 during the formation and development of radiation-induced skin ulcers and their effects on ulcer healing, a rat model which was locally irradiated with 60Co γ-rays was used, and another rat model of surgical skin wounds was made. Pathological changes were observed for 55 days. Immunohistochemistry,in situ hybridization and image analysis were performed to detect TGF-β1 and TGF-βR1 expression in the tissue of radiation skin ulcers and in surgical wounds. Results: Skin ulcers were found on day 14 after irradiation, and they were enlarged and deepened gradually during the observation period. In the irradiated skin, especially in the epidermal cells, fibroblasts and endothelial cells of the ulcer beds, the expression of TGF-β1 and TGF-βR1 was higher than that in normal skin. Compared with that in the surgical wound beds, the number of TGF-β1 and TGF-βR1 positive cells in radiation ulcer beds was obviously decreased, but TGF-β1 positive intensity was only slightly or not affected. Conclusion: After irradiation, the decreased expression of TGF-β1 and TGF-βR1 may play an important role in the formation, development and nonhealing mechanism of radiation skin ulcers.