Davis Thomas A, Amare Mihret, Naik Shruti, Kovalchuk Alexander L, Tadaki Douglas
Naval Medical Research Center, Silver Spring, MD 20910, USA.
Wound Repair Regen. 2007 Jul-Aug;15(4):577-88. doi: 10.1111/j.1524-475X.2007.00266.x.
Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. MRL/MpJ mice following ear-hole punch biopsies display accelerated healing and tissue regeneration. In this study, we characterized the healing responses in both MRL/MpJ and BALB/c mice following a 15% total body surface area full-thickness cutaneous burn injury. Macroscopic and histological observations show that delayed wound closure in MRL/MpJ mice is accompanied by an increase in edema, reduced neutrophil infiltration, and more prominent eschar. In vivo bromodeoxyuridine labeling showed no defect in keratinocyte proliferation and migration (reepithelialization). In comparison with BALB/c mice, MRL/MpJ wounds had greater collagen deposition, less granulation tissue formation, and contained fewer alpha-smooth muscle actin-positive myofibroblasts. An observed reduction in dermal neutrophil infiltration and myofibroblast development correlated with enhanced angiogenesis. Overall, BALB/c wounds contracted sooner and to a larger degree, resulting in a significant decrease in scar formation. Interestingly, MRL/MpJ mice showed overt abnormalities in hair follicle proliferation, morphogenesis, and subsequent hair regrowth postburn injury. No substantial evidence of tissue regeneration was observed in either BALB/c or MRL/MpJ wounds. Our results convincingly demonstrate that MRL/MpJ skin burn wounds heal with scar formation with delays in two critical wound healing events: wound closure, and myofibroblast development.
成年伤口修复始于初始炎症反应、上皮再形成以及永久性瘢痕的形成。MRL/MpJ小鼠在进行耳孔穿刺活检后表现出加速愈合和组织再生。在本研究中，我们对MRL/MpJ和BALB/c小鼠在15%体表面积全层皮肤烧伤后的愈合反应进行了特征描述。宏观和组织学观察表明，MRL/MpJ小鼠伤口愈合延迟伴随着水肿增加、中性粒细胞浸润减少以及焦痂更明显。体内溴脱氧尿苷标记显示角质形成细胞增殖和迁移（上皮再形成）无缺陷。与BALB/c小鼠相比，MRL/MpJ伤口的胶原沉积更多，肉芽组织形成更少，且α平滑肌肌动蛋白阳性肌成纤维细胞更少。观察到的真皮中性粒细胞浸润减少和成肌纤维细胞发育与血管生成增强相关。总体而言，BALB/c伤口收缩更快且程度更大，导致瘢痕形成显著减少。有趣的是，MRL/MpJ小鼠在烧伤后毛囊增殖、形态发生以及随后的毛发生长方面表现出明显异常。在BALB/c或MRL/MpJ伤口中均未观察到明显的组织再生证据。我们的结果令人信服地证明，MRL/MpJ皮肤烧伤伤口通过瘢痕形成愈合，在两个关键的伤口愈合事件中出现延迟：伤口闭合和成肌纤维细胞发育。
