Imegwu O, Chang T H, Steinberg J J, Levenson S M
Department of Surgery, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus and Montefiore Medical Center, Bronx, NY 10461, USA.
Wound Repair Regen. 1997 Oct-Dec;5(4):364-72. doi: 10.1046/j.1460-9568.1997.50411.x.
Cyclophosphamide given systemically to rats leads to impaired wound healing, characterized by decreases in the inflammatory reaction, fibroplasia, neovascularization, reparative collagen accumulation, and wound breaking strength. In contrast, the local application of Staphylococcus aureus peptidoglycan at the time of wounding increases all of these processes in normal rats. Accordingly, we hypothesized that inoculation of S. aureus peptidoglycan into wounds of cyclophosphamide-treated rats would ameliorate the otherwise impaired healing. Dorsal bilateral skin incisions and subcutaneous implantation of polyvinyl alcohol sponges (two on each side) were performed on male Sprague-Dawley rats receiving either saline or cyclophosphamide (24 mg/kg) intraperitoneally at the time of operation, on postoperative days 1, 2, 3, 4 (for rats killed on postoperative day 7), and also on day 8 (for rats killed on postoperative day 14). The incisions on one side were inoculated at the time of closure with 0.2 ml of saline solution, and the incisions on the other side with 6 mg S. aureus peptidoglycan in 0.2 ml saline solution (860 microg/cm incision). The sponges were instilled with 0.1 ml saline solution on the saline solution-instilled incision side or with S. aureus peptidoglycan 0.5 mg/sponge) in 0.1 ml saline solution on the other side. In control rats receiving saline solution intraperitoneally, incisions treated with S. aureus peptidoglycan were significantly stronger than saline solution-treated incisions by a factor of 1.8 at 1 week (p < 0.001); at 2 weeks the increase was small and not significant. Cardiac blood leukocytes and platelets fell markedly (90%) in cyclophosphamide- treated rats, and there was a decrease in wound breaking strength of their saline-treated incisions at both 7 and 14 days compared with saline solution-treated incisions of control rats. S. aureus peptidoglycan treatment of the wounds completely prevented this effect at 7 days, and partially at 14 days. Polyvinyl alcohol sponge reparative tissue hydroxyproline, 7 days after surgery, was decreased in cyclophosphamide-treated rats; this was completely prevented by S. aureus peptidoglycan treatment of the sponges. Histologically, the inflammatory response to the wounding, influx of macrophages and fibroblasts, angiogenesis, and collagen accumulation were all reduced at day 7 and 14 after surgery in the sponge reparative tissue of cyclophosphamide- treated rats; this was prevented by S. aureus peptidoglycan treatment of the sponges. In conclusion, a single local application of S. aureus peptidoglycan ameliorates cyclophosphamide-impaired wound healing.
对大鼠全身给予环磷酰胺会导致伤口愈合受损，其特征为炎症反应、纤维组织增生、新血管形成、修复性胶原积累及伤口抗张强度降低。相比之下，在受伤时局部应用金黄色葡萄球菌肽聚糖可促进正常大鼠上述所有过程。因此，我们推测将金黄色葡萄球菌肽聚糖接种到经环磷酰胺处理的大鼠伤口中可改善原本受损的愈合情况。对雄性Sprague-Dawley大鼠进行双侧背部皮肤切开及皮下植入聚乙烯醇海绵（每侧两个），手术时腹腔内注射生理盐水或环磷酰胺（24 mg/kg），术后第1、2、3、4天（用于术后第7天处死的大鼠）以及第8天（用于术后第14天处死的大鼠）也进行注射。一侧切口在缝合时注射0.2 ml生理盐水，另一侧切口注射含6 mg金黄色葡萄球菌肽聚糖的0.2 ml生理盐水（860 μg/cm切口）。在注射生理盐水的切口侧海绵中注入0.1 ml生理盐水，另一侧海绵中注入含0.5 mg金黄色葡萄球菌肽聚糖（每块海绵）的0.1 ml生理盐水。在腹腔内注射生理盐水的对照大鼠中，用金黄色葡萄球菌肽聚糖处理的切口在1周时的抗张强度比用生理盐水处理的切口显著高1.8倍（p < 0.001）；2周时增加幅度小且不显著。经环磷酰胺处理的大鼠心脏血液中的白细胞和血小板显著减少（90%），与对照大鼠经生理盐水处理的切口相比，其经生理盐水处理的切口在7天和14天时的伤口抗张强度均降低。用金黄色葡萄球菌肽聚糖处理伤口在7天时完全预防了这种影响，在14天时部分预防了这种影响。术后7天，经环磷酰胺处理的大鼠聚乙烯醇海绵修复组织中的羟脯氨酸减少；用金黄色葡萄球菌肽聚糖处理海绵可完全预防这种情况。组织学上，在术后第7天和第14天，经环磷酰胺处理的大鼠海绵修复组织中对伤口的炎症反应、巨噬细胞和成纤维细胞的流入、血管生成及胶原积累均减少；用金黄色葡萄球菌肽聚糖处理海绵可预防这种情况。总之，单次局部应用金黄色葡萄球菌肽聚糖可改善环磷酰胺所致的伤口愈合受损情况。
