Iocono J A, Krummel T M, Keefer K A, Allison G M, Paul H
Section of Pediatric Surgery, Department of Surgery, The Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Penn State Geisinger Health System, Hershey, Pa, USA.
Wound Repair Regen. 1998 Sep-Oct;6(5):442-8. doi: 10.1046/j.1524-475x.1998.60506.x.
The role for the metabolism of hyaluronic acid in the repair process is uncertain. Fetal dermal wounds do not heal by scarring and have sustained high levels of hyaluronic acid. In contrast, adult dermis is repaired by scarring and has less hyaluronic acid. Initially after injury, hyaluronic acid is elevated in both adult and fetal wounds, and although it remains elevated in fetal repair, it is rapidly degraded in adult wounds. The chronic addition of hyaluronic acid or hyaluronidase to polyvinyl alcohol sponge implants in adult mice was investigated in this study. Polyvinyl alcohol sponge implants containing a central reservoir were placed subcutaneously in the dorsum of adult male CD-1 mice. Mice were divided into three groups: a phosphate-buffered saline control, a 20 microgram hyaluronic acid treatment group, and a 10 U hyaluronidase treatment group. The central reservoir of each sponge implant received appropriate compound every 3 days for 2 weeks via transdermal injection and were then evaluated histologically. At 2 weeks, the cellular density and the quantity of granulation tissue deposition were the greatest in the hyaluronidase group and were lowest in the hyaluronic acid group. In addition, the organization of collagen fiber bundles was the most dense in the hyaluronidase group and least in the hyaluronic acid group. In a second experiment, polyvinyl alcohol sponge implants in mice received either phosphate-buffered saline solution or 20 microgram hyaluronic acid every 3 days for 1 week. On day 5, an aliquot of fluorescently tagged native collagen was injected into the sponges. Sponges were harvested at day 7, cryosections made, and the presence of autofluorescent collagen fibers assessed. The autofluorescent collagen fiber bundles in the phosphate-buffered saline solution group were organized in thick parallel bundles, whereas the collagen bundles from hyaluronic acid-treated implants were organized in fine lacelike structures. Chronic addition of hyaluronic acid appears to mimic the fetal dermal connective tissue matrix in which repair proceeds with diminished collagen deposition, organized in finer collagen fiber bundles in granulation tissue. On the other hand, the removal of hyaluronic acid by the chronic administration of hyaluronidase increases the amount of granulation tissue. Elevated levels of hyaluronic acid in granulation tissue appear to modulate the ability of resident fibroblasts to organize collagen fiber bundles.
透明质酸在修复过程中的代谢作用尚不确定。胎儿真皮伤口不会形成瘢痕愈合，且透明质酸水平持续较高。相比之下，成人真皮通过瘢痕形成进行修复，透明质酸含量较少。受伤后最初，成人和胎儿伤口中的透明质酸都会升高，尽管在胎儿修复过程中其仍保持升高，但在成人伤口中会迅速降解。本研究调查了在成年小鼠的聚乙烯醇海绵植入物中慢性添加透明质酸或透明质酸酶的情况。将含有中央储液器的聚乙烯醇海绵植入物皮下植入成年雄性CD - 1小鼠的背部。小鼠分为三组：磷酸盐缓冲盐水对照组、20微克透明质酸治疗组和10单位透明质酸酶治疗组。每个海绵植入物的中央储液器每3天通过经皮注射接受适当的化合物，持续2周，然后进行组织学评估。在2周时，透明质酸酶组的细胞密度和肉芽组织沉积量最大，透明质酸组最低。此外，透明质酸酶组的胶原纤维束排列最致密，透明质酸组最疏松。在第二个实验中，小鼠的聚乙烯醇海绵植入物每3天接受磷酸盐缓冲盐水溶液或20微克透明质酸，持续1周。在第5天，将一份荧光标记的天然胶原蛋白注入海绵中。在第7天收获海绵，制作冰冻切片，并评估自发荧光胶原纤维的存在情况。磷酸盐缓冲盐水溶液组的自发荧光胶原纤维束呈粗大平行束状排列，而透明质酸处理植入物的胶原束呈细小花边状结构排列。慢性添加透明质酸似乎模拟了胎儿真皮结缔组织基质，其中修复过程中胶原沉积减少，在肉芽组织中以更细的胶原纤维束形式组织起来。另一方面，通过慢性施用透明质酸酶去除透明质酸会增加肉芽组织的量。肉芽组织中升高的透明质酸水平似乎调节了驻留成纤维细胞组织胶原纤维束的能力。
