Metalloproteinase inhibitors and wound healing: a novel enhancer of wound strength.
Metalloproteinase inhibitors and wound healing: a novel enhancer of wound strength.
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DOI：
10.1016/s0039-6060(98)70154-0
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发表时间：
1998-08
期刊：
影响因子：
3.8
通讯作者：
M. Witte;F. Thornton;T. Kiyama;D. Efron;Gregory S. Schulz;L. Moldawer;A. Barbul
中科院分区：
文献类型：
--
作者：
M. Witte;F. Thornton;T. Kiyama;D. Efron;Gregory S. Schulz;L. Moldawer;A. Barbul
背景纤维强度是胶原蛋白合成和降解之间的平衡。胶原蛋白分解在伤口愈合中的作用尚不清楚。应用新型胶原酶抑制剂GM6001，研究胶原酶在创面愈合中的作用。雄性SD大鼠20只，随机分为GM6001(100 mg/kg体重)皮下注射和2mL生理盐水皮下注射。术后10d处死动物，测定新鲜创面撕裂强度、瘢痕和海绵羟脯氨酸含量、海绵中I型胶原基因表达。结果GM6001显著增加创面强度(422±59vs302±33g，P<；0.05)，而瘢痕胶原含量无明显变化。海绵肉芽肿组织中炎症渗出量、胶原含量及I型胶原基因表达均显著低于对照组。结论在创面急性愈合过程中，抑制基质金属蛋白酶活性可增强创面强度，即使创面的新胶原合成和炎症反应明显减少。这可以通过减少胶原周转或增加胶原成熟和交联度，或两者兼而有之来实现。(《外科》1998；124：464-70。)
BackgroundWound 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 by using GM6001, a novel inhibitor of MMPs.MethodsWe used the dosal skin incision model with implantation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (100 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–α [TNF-α] and transforming growth factor–β1 [TGF-β1]) profile were studied.ResultsGM6001 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.ConclusionsInhibition 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. (SURGERY 1998;124:464-70.)