Chang T H, Patel M, Watford A, Freundlich L, Steinberg J J
Department of Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461, USA.
Wound Repair Regen. 1997 Apr-Jun;5(2):184-90. doi: 10.1046/j.1524-475X.1997.50211.x.
An excess in glucocorticoid steroids, either from endogenous or exogenous sources, has been shown to inhibit wound repair. Key to this impairment is a diminution of the inflammatory response to wounding, fibroplasia, capillary formation, reparative tissue collagen accumulation, and wound breaking strength. Because a single local application at operation of nonviable Staphylococcus aureus or its peptidoglycan increases all of these processes in normal rats, we hypothesized that nonviable S. aureus and S. aureus peptidoglycan would each ameliorate glucocorticoid-induced impaired healing. Sprague-Dawley male rats aseptically received two 7 cm paravertebral skin incisions and underwent subcutaneous implantation of polyvinyl alcohol sponges. Two glucocorticoids were used: hydrocortisone, 8 mg intramuscularly, daily beginning 1 day before operation and continuing during the postoperative period; or a single dose of a long-acting preparation of methylprednisolone, 6 or 8 mg intramuscularly, on the day before operation. Controls received intramuscular injections of saline solution at the same respective times. At the time of the operation, one incision and the polyvinyl alcohol sponges on one side of the animal were instilled with saline solution while the incision and sponges on the opposite side were instilled with nonviable S. aureus (hydrocortisone study) or S. aureus peptidoglycan (two methylprednisolone studies). The data showed that, at postoperative day 7, the single local application at wounding of nonviable S. aureus or S. aureus peptidoglycan increased wound breaking strength in the control rats by factors of 1.6 in the hydrocortisone experiment and 1.4 and 1.6 in the methylprednisolone studies. These treatments prevented (in hydrocortisone-treated rats) or mitigated (in methylprednisolone-treated rats) the glucocorticoid-induced decrease in wound breaking strength. In addition, these treatments prevented the glucocorticoid-induced decreases in the inflammatory (largely mononuclear cells) response to wounding and in the accumulation within the polyvinyl alcohol sponge of reparative tissue fibroblasts, capillaries, and collagen.
内源性或外源性糖皮质激素过多已被证明会抑制伤口修复。这种损伤的关键在于对伤口的炎症反应、纤维组织增生、毛细血管形成、修复组织胶原蛋白积累以及伤口抗张强度的减弱。由于在正常大鼠手术时单次局部应用无活性金黄色葡萄球菌或其肽聚糖可增强所有这些过程，我们推测无活性金黄色葡萄球菌和金黄色葡萄球菌肽聚糖均可改善糖皮质激素诱导的愈合受损。将Sprague-Dawley雄性大鼠无菌处理后，在其脊柱旁做两个7厘米的皮肤切口，并皮下植入聚乙烯醇海绵。使用了两种糖皮质激素：氢化可的松，术前1天开始每天肌肉注射8毫克，术后持续使用；或在手术前一天单次肌肉注射6或8毫克长效甲泼尼龙制剂。对照组在相应时间接受肌肉注射生理盐水。手术时，给动物一侧的一个切口和聚乙烯醇海绵注入生理盐水，而另一侧的切口和海绵注入无活性金黄色葡萄球菌（氢化可的松研究）或金黄色葡萄球菌肽聚糖（两项甲泼尼龙研究）。数据显示，术后第7天，在对照组大鼠中，伤口处单次局部应用无活性金黄色葡萄球菌或金黄色葡萄球菌肽聚糖可使伤口抗张强度增加，在氢化可的松实验中增加了1.6倍，在甲泼尼龙研究中分别增加了1.4倍和1.6倍。这些处理预防了（在氢化可的松处理的大鼠中）或减轻了（在甲泼尼龙处理的大鼠中）糖皮质激素诱导的伤口抗张强度降低。此外，这些处理还预防了糖皮质激素诱导的对伤口的炎症反应（主要是单核细胞）降低以及聚乙烯醇海绵内修复组织成纤维细胞、毛细血管和胶原蛋白积累的减少。
