臺灣博碩士論文加值系統

乾癬是一種常見的慢性發炎性皮膚疾病，影響全球1-3％的人口，會經常復發，但不具傳染性。主要是由於皮膚中免疫系統的調節異常導致皮膚細胞的異常增生並產生厚皮屑。典型的乾癬皮膚病灶會發紅、變厚且有鱗狀斑塊浮起，全身多處皮膚部位皆可能發生。實際上，乾癬真正致病機制仍在研究中，其涉及多種免疫系統和皮膚系統之間的交互作用。然而，目前的治療方式效果有限，並且存在嚴重的副作用，因此，開發新穎藥物是必要且迫切的。根據我們先前的研究以及其他研究報導已經證實大豆萃取物與白楊素皆具有強效的抗氧化和抗發炎作用，在本篇研究中還證明了它們於治療皮膚發炎疾病中的應用潛力，有助於降低發炎反應及發炎性疼痛。透過體內試驗，我們發現局部應用IMQ (一種TLR 7促效劑，可活化免疫系統)，可以誘導且加重乾癬症狀。我們的研究結果顯示，大豆萃取物與白楊素可以明顯減輕小鼠模型中IMQ誘導之乾癬樣皮膚損傷，並改善IMQ誘導破壞之皮膚屏障功能。我們發現在IMQ處理前局部應用大豆萃取物與白楊素可明顯降低經表皮水分散失、發紅、血流速度和耳朵厚度，同時可增加表面皮膚含水量，減少表皮增生和發炎細胞的浸潤。透過體外試驗，我們發現大豆萃取物與白楊素可以減少人類表皮角質細胞中IL-22、IL-17A和TNF-α誘導之MAPK、NF-κB和JAK-STAT路徑的活化。更重要的是，大豆萃取物與白楊素可以減少TNF-α、IL-17A和IL-22誘導的CCL20和抗菌胜肽蛋白(AMPs)在表皮角質細胞之表現。這些實驗結果顯示，大豆萃取物與白楊素具有很大的潛力可作為抗乾癬製劑以及治療其他發炎性皮膚疾病。

Psoriasis is a common chronic inflammatory skin lesion. It affects 1–3% of the population worldwide and will be frequent recurrence, but not contagious. It is mainly due to the aberrant regulation of immune system in the skin that causes abnormal proliferation of skin cells and becomes thick dander. Typical psoriatic skin lesions are reddish, thick, scaly plaques that can occur on multiple skin sites all over the body. Actually, the real pathogenic mechanisms of psoriasis are still under study, which involves multiple interactions between the immune system and the skin system. However, the current therapeutic effects are limited, and there are severe side effects, therefore, it is necessary and urgent to develop new drugs. Our previous studies and other reports have demonstrated that both soybean extract and chrysin have strong antioxidant and anti-inflammatory effects. Their potential applications in the treatment of inflammation of the skin have also been reported in this study, which may help decrease inflammation and inflammatory pain. Through in vivo studies, we found that topical application of imiquimod (IMQ), a toll-like receptor (TLR)7 agonist and potent immune system activator, can induce and exacerbate psoriasis. Our results revealed that soybean extract and chrysin could obviously attenuate imiquimoid-induced psoriasis-like skin lesions in mice, and improve the imiquimod-induced disrupted skin barrier function. We found that the topical application of soybean extract and chrysin prior to IMQ treatment significantly decreased trans-epidermal water loss (TEWL), erythema, blood flow speed, and ear thickness, while it increased surface skin hydration, and attenuated epidermal hyperplasia and inflammatory cell infiltration. Through in vitro experiments, we found that soybean extract and chrysin can reduce IL-22, IL-17A, and TNF-α-induced MAPK, NF-κB, and JAK-STAT activation in normal human epidermal keratinocytes. Most importantly, soybean extract and chrysin could reduce TNF-α, IL-17A, and IL-22-induced CCL20 and antimicrobial peptides and proteins (AMPs) expression in epidermal keratinocytes. These results indicate that soybean extract and chrysin has great potential as an anti-psoriatic agent and in the treatment of other inflammatory skin diseases.

第一章、緒言 1
第二章、文獻回顧 3
第一節、皮膚結構 3
第二節、乾癬及其病生理分子作用機轉 5
第三節、現今治療乾癬之方式 15
第四節、植物多酚的分類與功用 21
第五節、類黃酮之功用 22
第三章、研究動機與目的 42
第四章、實驗材料與儀器 43
第一節、材料、試劑與藥品 43
第二節、儀器設備 45
第五章、實驗方法 46
第一節、倫理聲明守則 46
第二節、異黃酮之萃取方式 46
第三節、體內試驗 46
第四節、體外試驗 49
第六章、實驗結果 60
第一節、大豆萃取物於體內試驗與體外試驗對皮膚乾癬活性之影響 60
第二節、白楊素於體內試驗與體外試驗對皮膚乾癬活性之影響 70
第七章、研究討論 78
第八章、實驗結論 150
第九章、參考文獻 151
論文著作 173

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