MMP1，TIMP1在单纯及放射复合伤口愈合过程中的表达及对伤口愈合和组织改建的影响

目的：观察基质金属蛋白酶1（MMP1）、金属蛋白酶组织抑制因子1（TIMP1）在放射复合伤口愈合过程中表达的变化及对伤口愈合和组织改建的影响。方法：利用放射复合伤口动物模型，采用光镜、电镜、免疫组化及原位杂交等方法，动态观察伤口愈合有明显的损害作用，照射组织口较对照组伤口延迟6d愈合，在伤口愈合的炎症期和肉芽组织生长期，照射组新生表皮细胞中MMP1表达与对照组相近，在后期随着照射组伤口愈合的延迟其表达相对较高，在伤后3－14d，TIMP1在对照组新生表皮细胞中呈弱阳性，表皮覆盖皮呈阴性，而在照射组表皮覆盖前呈阴性或弱阳性。MMP1，TIMP1在照射组肉芽组织成纤维细胞、血管内皮细胞、巨噬细胞中表达明显降低，在愈合后期因辐射所致伤口愈合的延迟同样表现为表达时相拖后，结论：MMP1，TIMP1在放射复合伤口肉芽组织中表达明显降低直接影响细胞纤维、血形成和基质改建等病理过程，是辐射影响伤口合的重要机制之一。

Expression of MMP1 and TIMP1 in radiation combined wound healing and their effects on the healing process and tissue remodeling

Objective:To study the expression of MMP1 and TIMP1 in simple and radiation-combined wound healing and their effects on the healing process and tissue remodeling. Methods: A rat model of radiation-combined wound healing was used. Immunohistochemistry and in situ hybridization were performed which enabled the detection of MMP1 and TIMP1 expression in the healing process. Ultrastructural changes were observed with transmission EM. Results: The wound healing process was impaired and delayed. In rats receiving 25 Gy of gamma ray locally the irradiated wounds healed 6 days later than non-irradiated controls. The following changes in MMP1 and TIMP1 expression were found: (1) In the early inflammatory phase and in the period of granulation tissue formation, MMP1 expression in the newly-formed epidermis of irradiated wounds approximated that in the controls. Later, the epidermal expression of MMP1 in radiation wounds was comparatively increased with the delay of the healing process.On days 3 to 14 after wounding, TIMP1 was weakly positive in the proliferating keratinocytes of control wounds and became negative after epidermal covering, whereas no or only slight epidermal expression was detected in radiation wounds before epidermal covering.(2)MMP1 and TIMP　1 expression in radiation wounds was markedlydecreased in fibroblasts　, endotheliocytes and macrophages as compared with the controls. The expression phase was prolonged due to the delay of the healing process.Conclusions:The reduced expression of MMP1 and TIMP1 in granulation tissue retards such important processes as cell migration, angiogenesis and tissue remodeling, thus retarding the healing process. The expression of MMP1 in the newly-formed epidermis may help the process of reepithelialization,but in the late healing period, overexpression of MMP1 and decreased expression of TIMP1 in the epidermis may hinder the establishment of basal membrane and the formation of granulation tissue, and thus affect the matrix remodeling process.