Gray Steven D, Tritle Nathan, Li Wenhua
Division of Otolaryngology-Head and Neck Surgery, University of Utah Medical Center, Salt Lake City, Utah, USA.
Laryngoscope. 2003 Feb;113(2):237-42. doi: 10.1097/00005537-200302000-00008.
To evaluate the effect of topical and injected mitomycin on the expression of extracellular matrix proteins by fibroblasts in an early surgical wound model.
A prospective, controlled study in a rat wound model.
Six linear incisions were placed on the backs of each of three Sprague-Dawley rats, and polyvinyl alcohol sponges were implanted. Two control wounds were implanted with saline-soaked sponges. The two topical test group wounds were treated with 0.5 mg/mL topical mitomycin for 2 minutes, followed by sponge implantation. The two injection test group wounds were injected with 0.3 mL mitomycin (0.5 mg/mL) before incision and sponge implantation. Each incision was closed uniformly with 3-0 nylon suture. The sponges were harvested on the tenth postoperative day. Fibroblasts that had grown into the sponges were separated, and polymerase chain reaction analysis was used to quantify the expression of messenger RNA for several extracellular matrix proteins.
The expression of mRNA for some extracellular matrix proteins (elastase, hyaluronidase, and procollagen) was downregulated in the mitomycin test groups. The effect was more pronounced in the topical mitomycin test group compared with the injection test group. The wounds in the topical group were prone to dehiscence, and the wounds in the injection group demonstrated poor healing when compared with controls.
Mitomycin may inhibit wound healing by downregulating the gene expression for extracellular matrix proteins. This effect may be selective and may be more pronounced on inducible genes. Such findings prompt further studies regarding possible "best time" windows and selective gene suppression. The use of mitomycin may be limited in situations where wound integrity is necessary.
在早期手术伤口模型中评估局部和注射用丝裂霉素对成纤维细胞分泌细胞外基质蛋白表达的影响。
在大鼠伤口模型中进行的一项前瞻性对照研究。
在三只Sprague-Dawley大鼠的背部各做六条线性切口，并植入聚乙烯醇海绵。两个对照伤口植入用生理盐水浸湿的海绵。两个局部试验组伤口用0.5mg/mL局部丝裂霉素处理2分钟，然后植入海绵。两个注射试验组伤口在切口和植入海绵前注射0.3mL丝裂霉素（0.5mg/mL）。每个切口用3-0尼龙缝线均匀缝合。术后第10天取出海绵。分离长入海绵的成纤维细胞，并用聚合酶链反应分析定量几种细胞外基质蛋白信使核糖核酸的表达。
丝裂霉素试验组中一些细胞外基质蛋白（弹性蛋白酶、透明质酸酶和前胶原）的信使核糖核酸表达下调。与注射试验组相比，局部丝裂霉素试验组的效果更明显。与对照组相比，局部组的伤口易于裂开，注射组的伤口愈合较差。
丝裂霉素可能通过下调细胞外基质蛋白的基因表达来抑制伤口愈合。这种作用可能具有选择性，并且对诱导性基因的作用可能更明显。这些发现促使人们进一步研究可能的“最佳时间”窗口和选择性基因抑制。在需要保持伤口完整性的情况下，丝裂霉素的使用可能会受到限制。
