| 研究生: |
郭俊文 Guo, Jiun-Wen |
|---|---|
| 論文名稱: |
人類皮脂對皮膚屏障的影響及在脂漏性皮膚炎病理機轉中所扮演的角色 The effect of human sebum on skin barrier and its role in the pathogenesis of seborrheic dermatitis |
| 指導教授: |
蔡瑞真
Tsai, Jui-Chen 許漢銘 Sheu, Hamm-Ming |
| 學位類別: |
博士 Doctor |
| 系所名稱: |
醫學院 - 臨床藥學與藥物科技研究所 Institute of Clinical Pharmacy and Pharmaceutical sciences |
| 論文出版年: | 2014 |
| 畢業學年度: | 102 |
| 語文別: | 英文 |
| 論文頁數: | 71 |
| 中文關鍵詞: | 脂漏性皮膚炎 、皮脂 、皮脂成分 、脂肪酸 、皮膚屏障 |
| 外文關鍵詞: | seborrheic dermatitis, human sebum, sebum composition, free fatty acid, epidermal permeability barrier |
| 相關次數: | 點閱:147 下載:4 |
| 分享至: |
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脂漏性皮膚炎是最常見的反覆性慢性皮膚發炎疾病,主要發生在皮脂腺旺盛(皮脂漏)的區域。皮脂源自皮脂腺,是由多種脂質組成,具重要生理功能,過量分泌與許多臨床疾病相關。研究推測Malassezia 這一類的酵母菌會代謝皮脂成分中的三酸甘油脂的飽和脂肪酸而留下不飽和脂肪酸,而所留下的不飽和脂肪酸將會對皮膚產生刺激性並引發皮膚發炎反應。過去研究主要著重於單一脂肪酸對於皮膚屏障功能的的影響,然而對於生理性皮脂對皮膚屏障功能的影響以及皮脂在脂漏性皮膚炎病理機轉中所扮演角色的了解則是相當有限。
因此,本研究的主要目的在探討皮脂對於皮膚屏障的影響及皮脂在脂漏性皮膚炎病理機轉中所扮演的角色。首先,在無毛鼠背部塗抹人類皮脂的動物實驗中,我們證實人類皮脂對於無毛鼠會引起臨床上及組織學上的皮膚發炎現象,同時伴有經皮水分散失增加、角質層含水量降低、角質層脂肪排列零亂,並引發細胞素(cytokines)的釋放,如: TNF- α, IL-1α 以及IL-6等。以上之結果均顯示皮脂對皮膚障壁功能會有破壞的現象。接著藉由臨床表徵、組織學檢查以及血清IgE測量,我們證明皮脂所誘發的皮膚炎傾向於刺激性皮膚炎而非過敏性皮膚炎反應。進一步地,分析人類皮脂的脂肪酸組成,我們發現脂漏性皮膚炎患者以及皮脂長時間蓄積的狀況下,皮脂中的C18不飽和脂肪酸成分有增加的趨勢。
綜合上述,我們的研究結果指出皮脂會造成無毛鼠皮膚在功能上與結構上的傷害,以及引起一連串的發炎反應而形成刺激性皮膚炎。同時皮脂中的C18不飽和脂肪酸成分在脂漏性皮膚炎患者以及皮脂堆積的狀況下有增加的趨勢。這些結果指出了皮脂、接觸性皮膚炎與脂漏性皮膚炎的可能關連性,可能對脂漏性皮膚炎的治療有所幫助。
Seborrheic dermatitis (SD) is a common, recurrent, chronic inflammatory skin disorder. It generally arises in areas with high density of sebaceous glands. Human sebum is a complex mixture of lipids, which is secreted by mammalian sebaceous glands associated with hair follicles, and forms a fluid film over the skin surface. The functions of sebum have been known to soften the skin, to regulate the water content of the epidermis, to inhibit the growth of gram-positive bacteria and to prevent an invasion of external organisms. It was hypothesized that the Malassezia yeasts consumed the saturated fatty acids released from the triglycerides, and left behind the unsaturated fatty acids which cause inflammation and irritation. However, up to the present, there is only very limited information about the effect of sebum on skin barrier and its role in the pathogenesis of SD.
Two studies were designed to clarify the sebum effect on skin barrier and its role in pathogenesis in SD. In the first study, using a hairless mouse model, we clearly demonstrated the human sebum imparts detrimental effects on the skin permeability barrier both functionally and morphologically. The underlying mechanisms for sebum-induced barrier disruption are related directly to the interaction of sebum with the intracellular lipid lamellae of the stratum corneum (SC), thereby leading to increase the fluidity of SC intracellular lipids as demonstrated by ATR-FTIR spectroscopic measurement. Direct observation of the SC lipids by ruthenium tetroxide staining under electron microscope further confirm that intercellular lipid lamellae disorganization was the earliest morphological event following sebum application. The disruption of the skin barrier elicit an epidermal inflammatory cascade with the release of IL-1α, TNF-α, and IL-6 from the keratinocytes and later inflammatory cells infiltration in the upper epidermis. Although acute increase of these cytokines is crucial for skin barrier repair, in chronic barrier disruption, these cytokines cascade could have a harmful effect leading to cutaneous chronic inflammation. Supported by the epidermal TSLP staining and serum IgE data, and also in agreement with previous reports, we may conclude that sebum-induced dermatitis resembles irritant contact dermatitis rather than allergic dermatitis. In the second study, we reported the first human study to demonstrate elevated levels of oleic acid in both the SD sebum and in the control sebum collected 72 hr versus 24 hr post hair washing. Moreover, chronic applications of SD sebum and modified control sebum with similar oleic acid content onto mouse skin resulted in a higher TEWL value than application of control sebum. These results indicated possible involvement of C18 unsaturated fatty acid, and possibly others, in the pathogenesis of SD.
In summary, results from both studies in concert identified possible relationships between sebum, irritant contact dermatitis, and SD. These findings may have therapeutic implications for the treatment of SD.
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