微傷口對毛髮週期的影響

Abstract

禿髮是現代人很常見的困擾，目前雖有治療的藥物來改善禿髮的問題，但藥物常有副作用的伴隨，停藥後容易有復發的情形。 透過先前的研究發現傷口的癒合也有助於毛髮的生長，在小鼠的實驗上已經觀察到小傷口可以使毛囊縮短休止期，提前進入生長期，使毛囊再生，但確切的機制目前仍不清楚。 結合這兩種概念利用1550奈米點陣鉺玻璃雷射，有別於一般傳統雷射的大面積破壞使用點陣式能量輸出能量、分段治療的概念，利用1550奈米點陣鉺玻璃雷射不同的能量強度與每平方公分的雷射光束密度，希望可以找到透過控制性小傷口不要造成疤痕組織的情形下來建立誘發毛再生的模式，並探討毛囊再生的相關機制。 由實驗結果中發現在我們所建立的1550奈米點陣鉺玻璃雷射使毛囊提前進入生長期的模式中，毛囊幹細胞與次級毛胚在受到1550奈米點陣鉺玻璃雷射的刺激後有提前活化的現象，而毛囊型態變化順序與一般毛髮生長週期相同，只是在本模式使毛囊縮短了休止期提前進入生長期。經1550奈米點陣鉺玻璃雷射刺激後有引起發炎相關基因TNF-α、IL-1β、IL-1R1、VEGF-a,d的表現有顯著增加，但顯著增高的表現只在刺激後的一到三天。而發炎細胞中嗜中性白血球也在第一天有顯著的表現；巨噬細胞則在雷射刺激前後則無明顯的差異。 我們進一步探討將1550奈米點陣餌玻璃雷射刺激所引起表現量顯著差異的發炎相關的基因使用抑制劑或是轉殖基因鼠將這些基因抑制掉來觀察缺少這些基因是否對本模式毛囊提前進入生長期的現象有所影響。結果發現VEGF receptor受抑制後本模式則無法提前進入生長期。由實驗可知VEGF在本模式中扮演了很重要的關鍵。

Alopecia is a common disease. Although hair drug therapy can improve alopecia, there is relapse after discontinuation of drug. Previous studies have found that wounding was able to induce hair regrowth and in vitro study mentioned that specific small wound, different from large wound induced by shortening telogen, but the mechanism is still not clarified. In this work, we use the 1,550-nm fractional erbium glass laser dot-matrix energy output and segmented treatment, which is different from the traditional widespread destruction laser, to establish a small wound-induced hair regeneration model, without scar tissue formation. Results show that 1,550-nm fractional erbium glass laser can induce premature anagen entry by activating hair follicle stem cells and secondary hair germ. After the 1,550-nm fractional erbium glass laser stimulation, expression of inflammation-related genes including TNF-α, IL-1β, IL-1R1, VEGF-a, d significantly increased from 24hr to 72hr. Besides, neutrophil infiltration is observed at 24h. We further found that inhibiting VEGF receptor phosphorylation could block laser induced hair regeneration. Therefore, VEGF signaling plays an important role in micro-injury induced follicle regeneration.