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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 ,动态观察伤口愈合过程中MMP1,TIMP1mRNA转录及蛋白表达的变化。结果 :2 5Gy(γ射线 )局部照射对伤口愈合有明显的损害作用 ,照射组伤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 ,表皮覆盖后呈阴性 ,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迁移、血管形成和基质改建等病理过程 ,是辐射影响伤口愈合的重要机制之一。
OBJECTIVE: To observe the changes of matrix metalloproteinase 1 (MMP1) and tissue inhibitor of metalloproteinase 1 (TIMP1) during wound healing and their effect on wound healing and tissue remodeling. Methods: The changes of MMP1 and TIMP1mRNA transcription and protein expression in wound healing process were observed dynamically by light irradiation, electron microscope, immunohistochemistry and in situ hybridization. RESULTS: Local irradiation with 2 Gy (γ-ray) had a significant effect on wound healing. The wounds in the irradiated group healed 6 d later than those in the control group. In the wound healing inflammatory phase and the granulation tissue growth phase, the expression of MMP1 in irradiated epidermal cells was similar to that of the control group, with a relatively higher expression of MMP1 after the wound healing in the irradiated group was delayed. At 3 ~ 14 days after injury, TIMP1 was weakly positive in the control group of neonatal epidermal cells, negative after the epidermis was covered, and negative or weakly positive before the epidermis was covered by the irradiation group. The expressions of MMP1 and TIMP1 in granulation tissue fibroblasts, vascular endothelial cells and macrophages in irradiation group were significantly decreased. The delay of wound healing due to radiation in the later healing phase also showed the delayed expression. Conclusion: The decreased expression of MMP1 and TIMP1 in the granulation tissue of irradiated wounds directly affects the pathological process of cell migration, angiogenesis and matrix remodeling. It is one of the important mechanisms of radiation affecting wound healing.