準分子光(308nm)誘發分節型白斑色素恢復過程之機轉探討:利用皮膚血流變化及周邊交感神經反應為研究模式

The Mechanism of Excimer Light Induced Repigmentation in Segmental Vitiligo: Assessment of Cutaneous Blood Flow and Adrenoceptor Response

蘇雍順(Yung-Shun Su)

指導教授 ： 余幸司

高雄醫學大學/醫學院/醫學研究所/臨床醫學組/碩士(2014年)

摘要

白斑是一種最常見的後天慢性色素脫失疾病，原因是黑色素細胞遭受破壞。白斑可以分為非分節型白斑(non-segmental vitiligo)與分節型白斑(segmental vitiligo)。非分節型白斑被認為與皮膚的自體免疫攻擊黑色素細胞有關；分節型白斑是一種特殊型的白斑，其病灶分布於單側的神經節段上，機轉被認為與周邊交感神經機能異常有關。分節型白斑相較於非分節型白斑難治療，準分子光(波長308nm)在臨床上已被證實能有效地誘導白斑的色素恢復。本研究利用皮膚血流變化及周邊交感神經反應來探討準分子光誘發分節型白斑色素恢復過程之機轉。我們選取10位分節型白斑患者，每週接受準分子光治療2-3次，持續三個月。我們利用雷射都卜勒血流測量及離子導入三種擬交感神經試劑α1-agonist: phenylephrine、α2-agonist: clonidine及β-blocker: propranolol，評估準分子光治療前及治療後病灶部位皮膚的血流及交感神經反應。本研究發現分節型白斑病灶有皮膚血流量上升以及異常的α1及α2交感神經腎上腺接受器反應。在經過三個月的準分子光治療後，60%的病人可以達到>25%的色素回復，色素回復的病人的交感神經腎上腺接受器功能亦趨於正常。

過去的研究發現TNF-α能促進神經的存活及活化交感神經系統，IL-1能活化交感神經系統，IL-10的上升被認為可以促進T-regulatory細胞的分化與活化進而抑制黑色素細胞的破壞，vascular endothelial growth factor(VEGF)能保護神經及促進周邊交感神經軸突的生長及存活。因此可推測TNF-α、IL-1β、IL-10及VEGF可能在白斑的形成、色素回復及交感神經修復的過程扮演一定的角色。為進一步了解色素回復及交感神經腎上腺接受器功能恢復的可能機轉，我們抽取健康受試者的周邊血液單核細胞分別照射準分子光及低能量雷射。本研究發現照射準分子光後，TNF-α、IL-1β及VEGF的分泌有顯著的上升，而照射低能量雷射光的僅有VEGF有顯著上升。

總結，本研究證實準分子光可以有效地用來治療分節型白斑、誘發色素再生，並且讓皮膚交感神經的異常反應回復，其機轉有可能是透過TNF-α、IL-1β及VEGF的分泌及交感神經的修復。

關鍵字

分節型白斑 ； 準分子光 ； 離子導入 ； TNF-α ； IL-1β ； VEGF

並列摘要

Vitiligo, the most common acquired depigmentation disorder, is characterized by progressive loss of melanocytes. It has been proposed that two types of vitiligo exist from the clinical and pathophysiologic points of view. Non-segmental vitiligo is associated with autoimmune disease while segmental vitiligo results from the dysfunction of sympathetic nerves in the affected area. Comparing to non-segmental vitiligo, segmental vitiligo generally responds less favorably to phototherapy. Excimer light has been shown to be effective and able to induce repigmentation more rapidly. To evaluate the mechanism of excimer light induced repigmentation in segmental vitiligo, we utilized laser Doppler flowmetry and iontophoresis of α1-agonist: phenylephrine, α2-agonist: clonidine and β-blocker: propranolol to assess of cutaneous blood flow and adrenoceptor response. 10 segmental vitiligo patients were invited to participate in this study. The cutaneous blood flow and adrenoceptor response were investigated before and after 3-month regular excimer light treatment. Increased cutaneous blood flow and abnormal α1- and α2-adrenoreceptor function in segmental vitiligo lesions were noted. Upon 3-month excimer light treatment, 60% of patients achieved >25% repigmentation. Partial recovery of the sympathetic dysfunction was also noted.

TNF-α, IL-1β, IL-10 and vascular endothelial growth factor (VEGF) have been associated with vitiligo repigmentation and sympathetic nerve repairment. Peripheral blood mononuclear cells were collected from healthy volunteers and irradiated with excimer light and low level laser. Compared to control groups, supernatants from excimer group showed elevated TNF-α, IL-1β and VEGF, while those from low level laser group showed elevated VEGF only.

We concluded that excimer light could be an effective treatment for segmental vitiligo, possibly through the TNF-α, IL-1β and VEGF elevation and the partial repair of the sympathetic dysfunction.

並列關鍵字

segmental vitiligo ； excimer light ； iontophoresis ； TNF-α ； IL-1β ； VEGF

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