Nedelec B, Dodd C M, Scott P G, Ghahary A, Tredget E E
Departments of Surgery and Biochemistry; and the Division of Plastic Surgery and Critical Care, University of Alberta, Edmonton, Alberta, Canada.
Wound Repair Regen. 1998 May-Jun;6(3):202-12. doi: 10.1046/j.1524-475x.1998.60306.x.
Scar contraction following the healing of deep partial-thickness or full-thickness dermal injury is a leading cause of functional and cosmetic morbidity. The therapeutic use of interferon for the treatment of fibroproliferative disorders associated with scar contraction, including hypertrophic scar, has been suggested because of its antifibrotic properties. Treatment of fibroblasts with interferon has been shown to reduce the rate and extent of contraction using the in vitro fibroblast-populated collagen lattice model. In order to establish the effect of interferon-alpha2b on full-thickness wound contraction in vivo, osmotic pumps loaded with interferon or sterile saline were implanted intraperitoneally in guinea pigs. Seven days following implantation, six full-thickness punch biopsy wounds were created and were monitored by daily assessment of the wound. There was a significant reduction in the rate of wound contraction in the interferon-treated animals after day 3 (p < 0.01). Western blot analysis was used to quantitate selected cytoskeletal proteins in the normal skin and tissue biopsied from the wound at days 7, 14, and 21 postinjury. The amount of vimentin in the contracted wound increased following injury as compared with the amount present in normal skin (p < 0.0001); however, the relative amounts of the myofibroblast-associated cytoskeletal proteins alpha-smooth muscle actin and smooth muscle myosin were less than those found in normal, uninjured skin. By using vimentin to adjust the levels of cytoskeletal proteins for the increase in cellularity in the wounds, both alpha-smooth muscle actin and smooth muscle myosin significantly increased after closure of the wounds on day 14, as compared with the open-wound stage (day 7), before further reductions occurred with remodeling on day 21. Measurement of apoptotic cells using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay revealed an increase in apoptosis in the interferon-alpha2b-treated animals at 21 days following wounding (p < 0.001), which did not colocalize with alpha-smooth muscle actin staining. Taken together, these findings suggest that interferon-alpha2b inhibits wound contraction in vivo, not through an appreciable alteration in myofibroblast number or cytoskeletal protein expression, but possibly through a reduction in fibroblast cellularity by the induction of apoptosis.
深度部分厚度或全层皮肤损伤愈合后的瘢痕收缩是导致功能和美容问题的主要原因。由于干扰素具有抗纤维化特性，因此有人建议将其用于治疗与瘢痕收缩相关的纤维增生性疾病，包括肥厚性瘢痕。使用体外成纤维细胞填充胶原晶格模型已表明，用干扰素处理成纤维细胞可降低收缩速率和程度。为了确定干扰素-α2b对体内全层伤口收缩的影响，将装有干扰素或无菌盐水的渗透泵腹腔内植入豚鼠体内。植入7天后，制作6个全层打孔活检伤口，并通过每日评估伤口进行监测。在第3天之后，干扰素治疗组动物的伤口收缩速率显著降低（p < 0.01）。在损伤后第7天、14天和21天，使用蛋白质免疫印迹分析对从伤口处活检的正常皮肤和组织中的选定细胞骨架蛋白进行定量。与正常皮肤中的波形蛋白含量相比，收缩伤口中的波形蛋白含量在损伤后增加（p < 0.0001）；然而，成肌纤维细胞相关细胞骨架蛋白α-平滑肌肌动蛋白和平滑肌肌球蛋白的相对含量低于正常未受伤皮肤中的含量。通过使用波形蛋白来调整细胞骨架蛋白水平以适应伤口中细胞数量的增加，与开放伤口阶段（第7天）相比，在第14天伤口闭合后，α-平滑肌肌动蛋白和平滑肌肌球蛋白均显著增加，之后在第21天随着重塑进一步减少。使用末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法测量凋亡细胞，结果显示在受伤后21天，干扰素-α2b治疗组动物的凋亡增加（p < 0.001），且凋亡与α-平滑肌肌动蛋白染色不共定位。综上所述，这些发现表明，干扰素-α2b在体内抑制伤口收缩，并非通过明显改变成肌纤维细胞数量或细胞骨架蛋白表达，而是可能通过诱导凋亡来减少成纤维细胞数量。
