Qiu J G, Chang T H, Steinberg J J, Levenson S M
Departments of Surgery, Albert Enstein College of Medicine, Bronx, NY, USA.
Wound Repair Regen. 1998 Sep-Oct;6(5):449-56. doi: 10.1046/j.1524-475x.1998.60507.x.
Diabetes-induced impaired wound healing is characterized by inhibition of the inflammatory response to wounding, macrophage infiltration, angiogenesis, fibroplasia, reparative collagen accumulation, and wound breaking strength. Because all of these processes are accelerated in normal rats by a single local application at operation of Staphylococcus aureus peptidoglycan, we hypothesized that S. aureus peptidoglycan would prevent diabetes-induced impaired wound healing, despite persistent, untreated hyperglycemia, polydipsia, glycosuria, and polyuria. Sprague- Dawley male rats were divided into two groups. One group received an intraperitoneal injection of streptozotocin (65 mg/kg) in citrate solution; the other group received an intraperitoneal injection of an equivalent volume of citrate solution. Seventeen days after the injections, the diabetic and control rats received aseptically two 5.5-cm paravertebral incisions and subcutaneous implantation of six polyvinyl alcohol sponges, three on each side. On one side, each sponge contained 0.5 mg S. aureus peptidoglycan in 50 microliter saline solution, and the incision was inoculated along its length with 4.7 mg S. aureus peptidoglycan in 157 microliter saline solution (860 microgram/S. aureus peptidoglycan/cm incision); on the other side, the same respective volumes of saline were used. During the preoperative and postoperative periods, diabetic rats lost a small amount of weight (2%), were hyperglycemic (363 +/- 10 mg/100 ml blood), polydipsic, glycosuric, and polyuric, whereas the controls gained weight (25%) and were normoglycemic (104 +/- 5 mg/100 ml blood); these differences were significantly different (p <.001 in each case). In controls, S. aureus peptidoglycan inoculation increased wound breaking strength (by a factor of 2.0) and hydroxyproline content (by a factor of 1.4; p <.001 in each case); in diabetics, there were significant decreases in wound breaking strength (by a factor of 1.7) and hydroxyproline content (by a factor of 1.3) of saline solution-inoculated incisions and sponges compared with the wound breaking strength and hydroxyproline content of saline solution-inoculated incisions and sponges in controls (p <.02 and p <.001, respectively). These decreases were completely prevented when the incisions and polyvinyl alcohol sponges had been inoculated at operation with S. aureus peptidoglycan; S. aureus peptidoglycan inoculation in the diabetic rats increased wound breaking strength by a factor of 2.2 and sponge reparative tissue hydroxyproline by a factor of 1.6 (p <.001 in each case). Thus, diabetes-induced impaired wound healing was prevented completely by a single local instillation at operation of S. aureus peptidoglycan, despite persistent, untreated hyperglycemia, polydipsia, polyuria, and glycosuria.
糖尿病所致的伤口愈合受损表现为对伤口的炎症反应、巨噬细胞浸润、血管生成、纤维组织增生、修复性胶原积累及伤口抗张强度受到抑制。由于在正常大鼠中，通过在手术时单次局部应用金黄色葡萄球菌肽聚糖可加速所有这些过程，我们推测，尽管存在持续性未经治疗的高血糖、多饮、糖尿和多尿，金黄色葡萄球菌肽聚糖仍可预防糖尿病所致的伤口愈合受损。将雄性Sprague-Dawley大鼠分为两组。一组腹腔注射柠檬酸盐溶液中的链脲佐菌素（65 mg/kg）；另一组腹腔注射等量的柠檬酸盐溶液。注射17天后，糖尿病大鼠和对照大鼠无菌接受两个5.5厘米的椎旁切口，并在皮下植入6个聚乙烯醇海绵，每侧3个。一侧，每个海绵含50微升盐溶液中的0.5毫克金黄色葡萄球菌肽聚糖，切口沿其长度接种157微升盐溶液中的4.7毫克金黄色葡萄球菌肽聚糖（860微克/金黄色葡萄球菌肽聚糖/厘米切口）；另一侧，使用相同体积的盐水。在术前和术后期间，糖尿病大鼠体重略有下降（2%），血糖升高（363±10毫克/100毫升血液），有多饮、糖尿和多尿，而对照大鼠体重增加（25%），血糖正常（104±5毫克/100毫升血液）；这些差异具有显著性（每种情况p<0.001）。在对照大鼠中，接种金黄色葡萄球菌肽聚糖可增加伤口抗张强度（增加2.0倍）和羟脯氨酸含量（增加1.4倍；每种情况p<0.001）；在糖尿病大鼠中，与对照大鼠中接种盐溶液的切口和海绵的伤口抗张强度及羟脯氨酸含量相比，接种盐溶液的切口和海绵的伤口抗张强度显著降低（降低1.7倍），羟脯氨酸含量显著降低（降低1.3倍）（分别为p<0.02和p<0.001）。当在手术时切口和聚乙烯醇海绵接种金黄色葡萄球菌肽聚糖时，这些降低被完全预防；糖尿病大鼠接种金黄色葡萄球菌肽聚糖使伤口抗张强度增加2.2倍，海绵修复组织羟脯氨酸增加1.6倍（每种情况p<0.001）。因此，尽管存在持续性未经治疗的高血糖、多饮、多尿和糖尿，但在手术时单次局部滴注金黄色葡萄球菌肽聚糖可完全预防糖尿病所致的伤口愈合受损。
