Ehrlich H P, Buttle D J
Exp Mol Pathol. 1984 Apr;40(2):223-34. doi: 10.1016/0014-4800(84)90079-0.
The pathophysiological biology of human hypertrophic scar was examined in a long-term organ culture system. Fresh full-thickness, thin slices of scar were placed in petri dishes. Tissue was successfully maintained for 2 weeks in an environment made up of CMRL-1066 medium, fetal bovine serum, insulin, and hydrocortisone under an environment of 40% O2, 5% CO2, and 55% N2 at 37 degrees C on a rocking platform. Histologically the explants were viable and remained differentiated. The omission of hydrocortisone caused localized destruction of the connective tissue matrix under the epidermal layer. Transplanting the epidermis to the adipose surface of an explant before culturing in hydrocortisone-free medium, produced localized connective tissue matrix destruction only within the deep dermal layer. Removal of the epidermis before culturing in hydrocortisone-free medium produced no localized connective tissue matrix destruction. Culture medium from intact explants maintained in hydrocortisone-free media had higher levels of latent collagenase activity compared to epidermal free explants and intact explants in hydrocortisone-containing medium. This hypertrophic scar latent collagenase had a molecular weight estimated to be 33,000 by molecular-sieve chromatography. The active form of the enzyme had a molecular weight estimated to be 26,000. When examined by gel electrophoresis, activated collagenase cleaved types I and III native collagens, producing TC-A peptide fragments of alpha chains. Type V collagen was not cleaved by this enzyme. Metal chelators such as 1,10-phenanthroline blocked enzymatic activity. Serine and sulfhydryl proteolytic inhibitors showed no effects. Intact hypertrophic scar has the capacity to produce collagenase which appears responsible for the destruction of the connective tissue matrix of the scar. The production of hypertrophic scar collagenase is somehow controlled by the epidermis.
在长期器官培养系统中研究了人类增生性瘢痕的病理生理生物学。将新鲜的全层薄瘢痕切片置于培养皿中。在由CMRL - 1066培养基、胎牛血清、胰岛素和氢化可的松组成的环境中，于37摄氏度、40%氧气、5%二氧化碳和55%氮气的条件下，在摇摆平台上成功维持组织2周。组织学检查显示外植体存活且保持分化状态。去除氢化可的松会导致表皮层下结缔组织基质的局部破坏。在无氢化可的松培养基中培养前，将表皮移植到外植体的脂肪表面，仅在真皮深层产生局部结缔组织基质破坏。在无氢化可的松培养基中培养前去除表皮则不会产生局部结缔组织基质破坏。与不含表皮的外植体以及含氢化可的松培养基中的完整外植体相比，在无氢化可的松培养基中培养的完整外植体的培养基具有更高水平的潜在胶原酶活性。这种增生性瘢痕潜在胶原酶通过分子筛色谱法估计分子量为33,000。该酶的活性形式估计分子量为26,000。通过凝胶电泳检测时，活化的胶原酶可切割I型和III型天然胶原蛋白，产生α链的TC - A肽片段。V型胶原蛋白不会被该酶切割。金属螯合剂如1,10 - 菲咯啉可阻断酶活性。丝氨酸和巯基蛋白水解抑制剂无作用。完整的增生性瘢痕具有产生胶原酶的能力，这似乎是瘢痕结缔组织基质破坏的原因。增生性瘢痕胶原酶的产生在某种程度上受表皮控制。
