Cromack D T, Porras-Reyes B, Purdy J A, Pierce G F, Mustoe T A
Department of Surgery, Washington University Medical Center, St. Louis, Mo.
Surgery. 1993 Jan;113(1):36-42.
Transforming growth factor beta 1 (TGF-beta 1) is an effective accelerator of soft tissue repair in both normal and impaired healing models; however, its in vivo mechanism of action remains unclear. Modern radiation techniques can create unique healing deficits, allowing for a more specific definition of tissue response to growth factor therapy. In the rat linear skin incision model, cobalt 60 photon beam total body irradiation (TBI), 800 rads, causes a marked depression of circulating monocytes and largely spares the skin tissue. Megavoltage electron beam surface irradiation (SI), 2500 rads, markedly impairs surface healing while sparing the bone marrow. With these models of selective healing deficits, the ability of TGF-beta 1 to accelerate tissue repair directly in the absence of circulating macrophage precursors (TBI) or in the presence of damaged dermal fibroblasts (SI) was evaluated.
Adult male Sprague-Dawley rats were randomly assigned to groups of TBI, SI, or nonirradiated sham controls and received radiation 2 days before wounding. Paired linear full-thickness skin incisions were created and a single dose of TGF-beta 1 (2 micrograms/wound) or vehicle control was applied to each wound.
Both radiation techniques produced a marked healing deficit when assessed on postwounding days 7 and 12. TBI treatment was characterized by severe monocytopenia, confirmed by a tissue macrophage-specific immunohistochemical technique. On days 7 and 12 after wounding, TGF-beta 1 significantly accelerated soft tissue repair and wound-breaking strength in the TBI-treated rats, demonstrating an ability to directly promote the induction of collagen synthesis in the absence of monocytes/macrophages. In contrast, TGF-beta 1 was unable to reverse the SI-induced healing deficit characterized by impaired function of dermal fibroblasts.
These in vivo observations provide further evidence for a direct mechanism of action by TGF-beta 1 on collagen synthesis by wound fibroblasts during soft tissue repair.
转化生长因子β1（TGF-β1）在正常和受损愈合模型中都是软组织修复的有效促进剂；然而，其体内作用机制仍不清楚。现代放射技术可造成独特的愈合缺陷，从而更具体地界定组织对生长因子治疗的反应。在大鼠线性皮肤切口模型中，800拉德的钴60光子束全身照射（TBI）会导致循环单核细胞显著减少，而皮肤组织大多不受影响。2500拉德的兆伏电子束表面照射（SI）会显著损害表面愈合，同时使骨髓免受影响。利用这些选择性愈合缺陷模型，评估了TGF-β1在缺乏循环巨噬细胞前体（TBI）或存在受损真皮成纤维细胞（SI）的情况下直接加速组织修复的能力。
成年雄性Sprague-Dawley大鼠被随机分为TBI组、SI组或未照射的假手术对照组，并在受伤前2天接受辐射。制作成对的线性全层皮肤切口，每个伤口给予单剂量的TGF-β1（2微克/伤口）或载体对照。
在受伤后第7天和第12天评估时，两种放射技术均造成明显的愈合缺陷。TBI治疗的特征是严重单核细胞减少，这通过组织巨噬细胞特异性免疫组化技术得到证实。在受伤后第7天和第12天，TGF-β1显著加速了TBI治疗大鼠的软组织修复和伤口抗张强度，表明其在缺乏单核细胞/巨噬细胞的情况下有直接促进胶原合成诱导的能力。相比之下，TGF-β1无法逆转以真皮成纤维细胞功能受损为特征的SI诱导的愈合缺陷。
这些体内观察结果为TGF-β1在软组织修复过程中对伤口成纤维细胞胶原合成的直接作用机制提供了进一步证据。
