Levenson S M, Gruber D K, Gruber C, Lent R, Seifter E
J Trauma. 1981 Aug;21(8):632-44. doi: 10.1097/00005373-198108000-00007.
Experiments were conducted using non-enzymatic chemical agents (with emphasis on certain mercaptans), alone, in conjunction with enzymatic agents and/or other nonenzymatic chemicals for debridement of burns. Both in vitro (rats, pigs, humans) and in vivo (rats, pigs) tests were carried out. N-acetylcysteine, penicillamine and cysteine ethyl ester in low to moderate concentrations accelerate the debriding action of bromelain (an enzymatic preparation from pineapple stems) and in higher concentrations, N-acetylcysteine and penicillamine (cysteine ethyl ester was not tested) cause ready separation of the burn eschar from the underlying tissue before solubilization of the eschar is complete (rat) or has occurred (pig). Debridement of 3 degree burns of rats is complete within 4-6 hours; the take of immediately applied syngeneic skin grafts is complete and permanent. This is first time rapid debridement of 3 degree burns permitting immediate successful skin grafting has been accomplished with known defined chemicals. In pigs there is softening of the 3 degree burn eschar by N-acetylcysteine but little, if any, dissolution of the eschar. However, mechanical separation of the eschar from the underlying tissue is accomplished readily with a wooden throat stick with no bleeding. There is a change in color of the superficial layer of the underlying subcutaneous tissue from yellow-light brown to dark brown-black. The debrided areas begin to granulate promptly. The healing of deep dermal burns of pigs is hastened by the application of N-acetylcysteine for a day (beginning 24 hours after burning) while the healing of moderately deep dermal burns is not modified. Unburned skin is not damaged. There is no apparent systemic toxicity associated with the use of N-acetylcysteine for debridement of 10-15% b.s.a. 3 degree burns of rats or 15-20% b.s.a. 3 degree burns of pigs. Major emphasis has been on N-acetylcysteine because of the potential adverse secondary effect of penicillamine and cysteine ethyl ester; N-acetylcysteine is readily metabolized. The use of a keratolytic agent prior to the application of N-acetylcysteine hastens the latter's action. Sulfamylon and sulfadiazine can be used with N-acetylcysteine without interfering with its debriding action. The effects of the mercaptans are likely due largely to their ability to depolymerize connective tissue proteoglycans and proteins, especially at the interface between living and dead tissue.
使用非酶化学试剂（重点是某些硫醇）单独、与酶试剂和/或其他非酶化学物质联合进行烧伤清创实验。进行了体外（大鼠、猪、人）和体内（大鼠、猪）试验。低至中等浓度的N - 乙酰半胱氨酸、青霉胺和半胱氨酸乙酯可加速菠萝蛋白酶（一种从菠萝茎中提取的酶制剂）的清创作用，而高浓度时，N - 乙酰半胱氨酸和青霉胺（未测试半胱氨酸乙酯）在焦痂完全溶解（大鼠）或已经溶解（猪）之前就能使烧伤焦痂与下层组织轻易分离。大鼠三度烧伤的清创在4 - 6小时内完成；立即移植的同基因皮肤移植成功且永久存活。这是首次使用已知的特定化学物质实现三度烧伤的快速清创并允许立即成功进行皮肤移植。在猪身上，N - 乙酰半胱氨酸可使三度烧伤焦痂软化，但焦痂几乎没有溶解（如果有也很少）。然而，用木制压舌板很容易将焦痂与下层组织机械分离且不出血。下层皮下组织表层颜色从淡黄棕色变为深棕黑色。清创区域迅速开始形成肉芽。在猪身上，烧伤24小时后开始应用N - 乙酰半胱氨酸一天可加速深二度烧伤的愈合，而对中深度二度烧伤的愈合没有影响。未烧伤的皮肤未受损。使用N - 乙酰半胱氨酸对大鼠10 - 15%体表面积的三度烧伤或猪15 - 20%体表面积的三度烧伤进行清创，未发现明显的全身毒性。由于青霉胺和半胱氨酸乙酯可能产生不良的继发效应，所以主要重点研究了N - 乙酰半胱氨酸；N - 乙酰半胱氨酸易于代谢。在应用N - 乙酰半胱氨酸之前使用角质溶解剂可加速其作用。磺胺米隆和磺胺嘧啶可与N - 乙酰半胱氨酸一起使用而不干扰其清创作用。硫醇的作用可能主要归因于它们使结缔组织蛋白聚糖和蛋白质解聚的能力，尤其是在活组织和死组织的界面处。
