Gu Qingyang, Wang Dewen, Gao Yabing, Zhou Jie, Peng Ruiyun, Cui Yufang, Xia Guowei, Qing Quanhong, Yang Hong, Liu Jie, Zhao Meilan
Department of Pathology, Beijing Institute of Radiation Medicine, China.
J Environ Pathol Toxicol Oncol. 2002;21(1):71-8.
Radiation-impaired wound is characterized by delayed healing, nonhealing, and carcinogenesis. The mechanism remains unclear. Matrix metalloproteinases (MMPs) are one family of key regulators of the process of wound healing. Their abnormal expression plays important roles in the formation of some chronic skin ulcers. The objective of this project was to study the expression of MMP1 in surgical and radiation-impaired wound healing and its effects on the healing process and tissue remodeling. A rat model of radiation-impaired wound healing was used. Routine light microscopy, electron microscopy, immunohistochemistry, and in situ hybridization, all of which enabled the detection of MMP1 expression during the healing process, were performed. The wound healing process was impaired and delayed. In rats receiving 25Gy gamma-ray locally, the irradiated wounds healed 6 days later than the nonirradiated controls. The following changes in MMP1 expression were found: (1) In the early inflammatory phase and in the period of granulation tissue formation, MMP1 expression was only slightly if at all affected in the newly formed epidermis of irradiated wounds compared with controls. Later, the epidermal expression of MMP1 in radiation wounds was comparatively increased following the delay of the healing process. (2) MMP1 expression in irradiated wounds was markedly decreased in fibroblasts, endothelial cells, and macrophages compared with controls. The expression phase was prolonged because of the delay of the healing process. The reduced expression of MMP1 in granulation tissue retards such important processes as cell migration, angiogenesis, and tissue remodeling, thus slowing the healing process. The expression ofMMP1 in the proliferating keratinocytes may help re-epithelialization. However, in the late healing period, overexpression of MMP1 in the epidermis may hinder the establishment of basal membrane and the formation of granulation tissue, and affect the tissue remodeling process.
放射性损伤伤口的特点是愈合延迟、不愈合和致癌。其机制尚不清楚。基质金属蛋白酶（MMPs）是伤口愈合过程中的一类关键调节因子。它们的异常表达在一些慢性皮肤溃疡的形成中起重要作用。本项目的目的是研究MMP1在手术和放射性损伤伤口愈合中的表达及其对愈合过程和组织重塑的影响。采用放射性损伤伤口愈合的大鼠模型。进行了常规光学显微镜、电子显微镜、免疫组织化学和原位杂交，所有这些都能检测愈合过程中MMP1的表达。伤口愈合过程受到损害并延迟。在局部接受25Gyγ射线照射的大鼠中，照射伤口比未照射的对照组晚6天愈合。发现MMP1表达有以下变化：（1）在早期炎症阶段和肉芽组织形成期，与对照组相比，照射伤口新形成的表皮中MMP1表达即使有影响也非常轻微。后来，随着愈合过程的延迟，放射性伤口中MMP1的表皮表达相对增加。（2）与对照组相比，照射伤口中成纤维细胞、内皮细胞和巨噬细胞中的MMP1表达明显降低。由于愈合过程的延迟，表达阶段延长。肉芽组织中MMP1表达的降低阻碍了细胞迁移、血管生成和组织重塑等重要过程，从而减缓了愈合过程。增殖性角质形成细胞中MMP1的表达可能有助于重新上皮化。然而，在愈合后期，表皮中MMP1的过度表达可能会阻碍基底膜的建立和肉芽组织的形成，并影响组织重塑过程。
