Witte M B, Thornton F J, Kiyama T, Efron D T, Schulz G S, Moldawer L L, Barbul A
Department of Surgery, Sinai Hospital of Baltimore, MD 21215, USA.
Surgery. 1998 Aug;124(2):464-70.
Wound strength is a balance between collagen synthesis and degradation. The role of collagen breakdown in wound healing is still not well understood. We investigated the role of collagenases (metalloproteinases [MMPs]) in wound healing in using GM6001, a novel inhibitor of MMPs.
We used the dorsal skin incision model with implantation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (10 mg/kg body weight) or 2 mL saline subcutaneously. Ten days after operation the animals were killed and fresh wound breaking strength, scar and sponge hydroxyproline content, and collagen type I gene expression in sponges were assayed. In addition, the inflammatory response and the wound fluid cytokine (tumor necrosis factor-alpha [TNF-alpha] and transforming growth factor-beta 1 [TGF-beta 1]) profile were studied.
GM6001 significantly increased wound strength (422 +/- 59 vs 302 +/- 33 g, P < .05), whereas scar collagen content did not differ. In the sponge granulomas the inflammatory infiltrate, the collagen content, and the collagen type I gene expression were all significantly decreased by GM6001.
Inhibition of MMP activity during acute wound healing enhances wound strength even though new collagen synthesis and the inflammatory response are significantly decreased. This could be achieved by decreasing collagen turnover or increasing collagen maturation and crosslinking, or both.
伤口强度是胶原蛋白合成与降解之间的平衡。胶原蛋白分解在伤口愈合中的作用仍未得到充分理解。我们使用新型基质金属蛋白酶（MMPs）抑制剂GM6001研究了胶原酶（MMPs）在伤口愈合中的作用。
我们采用植入聚乙烯醇海绵的背部皮肤切口模型。20只雄性Sprague-Dawley大鼠被随机分配皮下注射GM6001（10mg/kg体重）或2ml生理盐水。术后10天处死动物，测定新鲜伤口的抗张强度、瘢痕和海绵中的羟脯氨酸含量以及海绵中I型胶原基因的表达。此外，还研究了炎症反应和伤口液细胞因子（肿瘤坏死因子-α [TNF-α] 和转化生长因子-β1 [TGF-β1]）谱。
GM6001显著提高了伤口强度（422±59 vs 302±33g，P <.05），而瘢痕胶原蛋白含量无差异。在海绵肉芽肿中，GM6001显著降低了炎症浸润、胶原蛋白含量和I型胶原基因表达。
在急性伤口愈合过程中抑制MMP活性可增强伤口强度，即使新胶原蛋白合成和炎症反应显著降低。这可以通过减少胶原蛋白周转或增加胶原蛋白成熟和交联，或两者兼而有之来实现。
