四種海豚科動物全層皮膚傷口癒合中色素恢復差異之組織病理學研究

Abstract

鯨豚的皮膚有很強的自我修復能力，即使是很深的傷口，也常常能在海水環境中自然癒合，不容易感染或留下疤痕。然而，皮膚損傷後的色素恢復機制尚不清楚，特別是在癒合後仍持續低色素沉澱的傷口中。儘管部分鯨豚物種已觀察到色素還原現象，但黑色素細胞在傷口癒合過程中的細胞層次機制，以及不同物種之間的色素還原差異，尚缺乏系統性探討。本研究分析了幾種不同海豚（糙齒海豚、小虎鯨、瑞氏海豚和弗氏海豚）在皮膚傷口癒合過程中的黑色素變化，並進一步探討導致傷口持續低色素沉澱的潛在機制。本研究中以Fontana–Masson染色及免疫組織化學方法評估黑色素細胞的數量、分布及與表皮的附著情形，也針對細胞間的連接蛋白 E-cadherin 以及抑制黑色素功能的 Dickkopf-1（DKK1）蛋白之表現進行分析，以探討其與低色素沉澱傷口之相關性。結果顯示，糙齒海豚（Steno bredanensis）、小虎鯨（Feresa attenuata）在腹側傷口中常見持續性低色素沉澱，而瑞氏海豚（Grampus griseus）在腹側與背側傷口皆可觀察到類似現象。這種穩定存在的低色素性傷口，在已發表的鯨豚組織學研究中尚不常見，也是本研究的一項重要觀察。這些傷口區域伴隨黑色素細胞密度下降及其由基底層脫離至上皮表層的現象。細胞間連結與訊號表現亦受到影響，包括E-cadherin訊號減弱及早期癒合階段DKK1表現上升。相較之下，弗氏海豚（Lagenodelphis hosei）則展現良好的色素還原能力，傷口中黑色素細胞數量豐富，並具有較強的E-cadherin訊號表現。這些證據皆表明不同海豚科物種間在皮膚色素恢復的能力上的顯著差異，其中細胞黏連不穩定、黑色素細胞脫離或受抑制性訊號干擾，都可能是部分物種傷口低色素沉澱的成因。這項研究提供關於鯨豚色素還原的比較性資料，亦可為治療如人類白斑症等色素異常疾病及鯨豚傷口照護策略帶來啟發。

Cetaceans possess an exceptional capacity for wound healing in a marine environment and are frequently able to recover from deep skin injuries without infection or scarring. However, the mechanisms regulating post-injury pigmentation remain unclear, particularly in cases where healed wounds persist as white areas. While repigmentation has been observed in some cetaceans, the cellular basis of melanocyte behavior and interspecies differences in pigment restoration have not been systematically investigated. This study aimed to characterize melanocyte distribution and repigmentation dynamics in full-thickness wounds across multiple delphinid species, with a focus on understanding why certain wounds remain hypopigmented. To investigate potential mechanisms underlying these differences, we examined melanocyte number, morphology, and epidermal adhesion using Fontana–Masson staining, and immunohistochemistry. The analysis also included assessment of suprabasal melanocytes, E-cadherin distribution, and melanocyte-specific markers across wound stages. Additionally, Dickkopf-1 (DKK1), a Wnt pathway antagonist known to suppress melanocyte function, was evaluated for its potential involvement in repigmentation failure. Results showed that rough-toothed dolphins (Steno bredanensis) and pygmy killer whales (Feresa attenuata) commonly exhibited persistent hypopigmentation in ventral wounds, while Risso’s dolphins (Grampus griseus) displayed similar features in both ventral and dorsal wounds. These depigmented areas were characterized by reduced melanocyte density and suprabasal detachment. Such a persistent hypopigmented wound pattern has been rarely documented in histological studies of cetacean wound healing. These wounds also showed weakened E-cadherin expression and elevated DKK1 levels, particularly in the early stages of healing. In contrast, Fraser’s dolphins (Lagenodelphis hosei) demonstrated successful repigmentation, characterized by abundant melanocytes spanning both basal and suprabasal layers and stronger E-cadherin signals. These findings highlight species-specific differences in melanocyte behavior and suggest that impaired adhesion, detachment, or inhibitory signaling may underlie hypopigmentation in some delphinids. This study provides a comparative framework for understanding pigment regeneration in cetaceans and offers new insights into potential therapeutic strategies for treating pigmentary disorders such as vitiligo and for improving wound care in cetaceans.