MMP1、TIMP1在放射复合伤口愈合过程中的表达及对伤口愈合过程的影响(英文)

利用放射复合伤口动物模型，动态观察伤口愈合过程中MMP1，TIMP1 mRNA转录及蛋白表达的变化及基对伤口愈合和组织改建的影响。结果显示：25Gy(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与TIMP1在照射组肉芽组织成纤维细胞、血管内皮细胞、巨噬细胞中表达较对照组明显降低，在愈合后期因辐射所致伤口愈合的延迟其表达时相拖后。结果表明：辐射所致MMP1与TIMP1在伤口肉芽组织中表达明显降低，直接影响迁移、血管形成和瘢痕组织形成等病理过程，是辐射影响伤口愈合的重要机制之一。

EXPRESSION OF MMP1 AND TIMP1 IN THE HEALING PROCESS OF GENERAL AND RADIATION-COMBINED WOUNDS AND ITS EFFECTS ON THIS PROCESS

A rat model of rediation combined wound hea1ing was used,and routine light microscopy observation, electron microscopy observation, immuno histochemistry, and in situ hybridization were performed to study MMPl and TIMP1 expression during the healing process. The wound healing process was impaired and delayed. After irradiation for rats receiving 25Gy Gamma ray locally the irradiated wounds healed 6 days later than non-irradiated controls. The folfowing changes of MMP1 and TIMP1 expression were found: (1) In the early inflammatory phase and in the period of granulation tissue formation, MMP1 expression was only slight, if affected at all in the newly formed epidermis of irradiated wounds. Later, the epidermal expression of MMP1 in radiation wounds was comparatively increased following the delay of the heallng process. From the 3rd day to 14th day after wounding, TIMP1 was weakly positive in the proliferating keratinocytes of control wounds and became negative after epidermal covering, whereas no or only slight epiderma expression was detected in the irradiated wounds before epidermal covering. (2) Compared to controls, MMP1 and TIMP1 expression in irradiated wounds was markedly decreased in fibroblasts, endotheliocytes and macrophages. The expression phase was prolonged due to the delay of the healing process. We conclude that the reduced expression of MMP1 and TIMP1 in granulation tissue of irradiated wounds retards such important processes as cell migration and angiogenesis, and thus s1ow 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 TIMP 1 in the epidermis may hinder the establishment of basal membrane and scar formation.