臺灣博碩士論文加值系統

異位性皮膚炎 (Atopic dermatitis, AD)，是一種過敏性皮膚疾病。全球約有五分之一的嬰幼兒人口受到該疾病的影響，典型的症狀為皮膚紅腫、發癢，經由搔抓引發傷口惡化。目前治療AD多使用類固醇藥物，但長期使用易有副作用。蛹蟲草是一種生長在昆蟲或昆蟲幼蟲上的真菌，其多種藥理活性而具有廣泛的醫學應用，包括抗氧化、降血糖、降血脂、抗炎、抗腫瘤、抗菌和抗真菌活性。本研究使用蛹蟲草菌絲體水萃萃取物 (Cordyceps militaris Mycelium water extract, CMMw)、蛹蟲草菌絲體酒萃萃取物 (Cordyceps militaris Mycelium ethanol extract, CMMe) 以及蛹蟲草子實體水萃萃取物 (Cordyceps militaris Fruiting body water extract, CMFw) 、蛹蟲草子實體酒萃萃取物 (Cordyceps militaris Fruiting body ethanol extract, CMFe) 作為樣品，藉由細胞實驗與動物實驗，探討其在細胞及動物體中對於過敏及 AD 相關之作用。本研究利用化合物 48/80 (Compound 48/80) 誘導進行 P815 肥大細胞與 CM 共同培養的脫顆粒實驗。實驗結果顯示，樣品中的蛹蟲草子實體有較高之預防細胞脫顆粒之功效。動物實驗則參考細胞實驗之結果，從四種樣品中選擇產量穩定、效果優秀之 CMFw 用於動物實驗。實驗結果顯示，蛹蟲草子實體水萃物 (CMFw) 能抑制 AD 誘導之 BALB/c 小鼠的背部皮膚角質層間距，還能調節免疫系統中第一型輔助型T細胞 (Helper T cell type 1, Th1) 及 Th2 之間的平衡，達到改善 AD 之效果。

Atopic dermatitis (AD) is an allergic skin disease. About one-fifth of the world's infants and children are affected by the disease. Typical symptoms are red, swollen, itchy skin that worsens through scratching. At present, steroid drugs are mostly used to treat AD, but long-term use is prone to side effects. Cordyceps militaris is a fungus that grows on insects or insect larvae and has a wide range of medical applications due to its multiple pharmacological activities, including antioxidant, hypoglycemic, hypolipidemic, anti-inflammatory, anti-tumor, antibacterial and antifungal activities. This study used Cordyceps militaris Mycelium water extract (CMMw), Cordyceps militaris Mycelium ethanol extract (CMMe), and Cordyceps militaris fruiting body water extract (CMFw) and Cordyceps militaris fruiting body ethanol extract (CMFe) were used as samples to explore their effects on allergies and allergies in cells and animals through cell experiments and animal experiments. AD-related effects. In this study, Compound 48/80 was used to induce degranulation experiments on P815 mast cells co-cultured with CM. Experimental results show that the Cordyceps militaris fruiting bodies in the sample have a high efficacy in preventing cell degranulation. For animal experiments, refer to the results of cell experiments, and select CMFw with stable yield and excellent effect from the four samples for animal experiments. Experimental results show that CMFw can inhibit the distance between the stratum corneum of the back skin of AD-induced BALB/c mice, and can also regulate the relationship between Helper T cell type 1 (Th1) and Th2 in the immune system. The balance among them can achieve the effect of improving AD.

摘要 ……………………………………………………………….…...…. I
Abstract ……………………………………………………….…….…… II
目錄 …………………………………………………………….……….. III
圖目錄 ………………………………………………………………..… VII
表目錄 ………..…………………………………………………………VIII
前言 ………….………………………………………………………….…. 1
貳、文獻回顧 …….……………………………………..………...…….…. 2
一、皮膚的構造及功能 ………………………..……..……….…… 2
1. 表皮 …………………………………………………….……... 2
1-1 角質層 ……………………………………….………. 2
1-2 透明層 ……………………………………….………. 2
1-3 顆粒層 ……………………………………….………. 2
1-4 棘狀層 ……………………………………….………. 3
1-5 基底層 ……………………………………….………. 3
1-6 基底膜帶 …………………………………………..… 3
2. 真皮 …………………………………………………… 3
2-1 乳頭層 ……………………………………..……….... 3
2-2 網狀層 ……………………………………………….. 4
二、異位性皮膚炎 ………………………………………………..... 4
1. 異位性皮膚炎介紹 ……………………………………….…... 4
2. 異位性皮膚炎之病因及機制 …………………………….…... 4
3. 異位性皮膚炎之診斷方式 …………………………………… 5
4. 異位皮膚炎之治療藥物 ……………………………………… 5
4-1 皮質類固醇 ………………………………………….. 5
4-2 抗組織胺藥物 ……………………………………..… 6
4-3 免疫抑制劑 ………………………………………….. 6
三、肥大細胞脫顆粒作用 ………………………………………… 6
四、化合物 48/80 (Compound 48/80) ……………………………. 7
五、誘導異位性皮膚炎之動物模式 ……………………………… 7
六、經表皮致敏誘發異位性皮膚炎模型 ………………………… 7
1. 卵白蛋白 ……………………………………………………... 7
2. 居家塵蟎 ……………………………………………………... 8
3. 半抗原 ………………………………………………………... 8
4. 超級抗原 …………..………………………….………..…….. 8
5. 食品過敏小鼠模型 …………………………...……………… 8
七、基因工程小鼠之異位性皮膚炎模型 ……………………………. 9
八、自發性異位性皮膚炎小鼠模型 ……………………………….… 9
九、蛹蟲草 (Cordyceps militaris) 介紹 …………………....………. 9
1. 冬蟲夏草之生物學特性 …………………………………….... 9
2. 冬蟲夏草於傳統上之運用與歷史 …………………….……. 10
3. 蟲草的生理活性 …………………………………………..… 10
3-1 蛹蟲草菌絲體 (Mycelia) 與子實體 (Fruiting body) 之比較 …………………………………………………………… 10
3-2 野生蛹蟲草與人工栽植蛹蟲草之比較 ……………..... 11
3-3 蛹蟲草菌絲體水萃與酒萃之特性 ……………………. 11
3-4 蛹蟲草子實體水萃與酒萃物抗癌之功效 ………. 12
3-5 蛹蟲草菌絲體水萃物改善氣喘之功效 ………………. 12
3-6 蛹蟲草菌絲體水萃物抗氧化之功效 …………………. 12
3-7 蛹蟲草菌絲體水萃物抗炎化之功效 …………………. 12
3-8 蛹蟲草菌絲體水萃物改善腸道之作用 …………….… 13
參、實驗設計 …………………………………………………………… 14
一、蛹蟲草萃取與特性分析 …………………………………..……. 14
二、細胞實驗 (In vitro) …………………………………………...… 14
二、動物實驗 (In vivo) …………………………………………….... 15
肆、實驗材料與方法 ………………………………………………….... 16
一、實驗材料 ………………………………………………………... 16
1-1. 樣品原料來源 ………………………………………………... 16
1-2. 化學成分分析標準品 ………...……………………………… 16
1-3. 抗氧化能力試驗 ……………………………………………... 16
1-4. 實驗細胞株 ………………………………………………..…. 17
1-5. 細胞培養之培養基 ……………………………..……………. 17
1-6. 細胞存活率試劑 ……………………………….…………….. 17
1-7. 一氧化氮 (NO) 含量測定分析試劑 …………………..…… 17
1-8. 酵素連結免疫吸附相關試劑 ………………………...……… 17
1-9. P815 脫顆粒誘導試劑 ……………….……………….…...… 18
1-10. 實驗動物 …………………………………………..….…….. 18
1-11. 病理組織切片 …………………………………………….… 18
二、儀器設備 ………………………………………………………... 20
三、實驗方法 ……………………………………………...………… 21
3-1. 蛹蟲草菌絲體、子實體萃取物製備 ……………………….. 21
3-1-1. 蛹蟲草菌絲體、子實體熱水萃取物 …………….... 21
3-1-2. 蛹蟲草菌絲體、子實體乙醇萃取物 …………..….. 21
3-2. 樣品特性分析 ……………………………………………….. 21
3-2-1. 總醣含量 ……………….……………...…………… 21
3-2-2. 粗蛋白含量 ………………………………………… 21
3-3. 蛹蟲草萃取物抗氧化能力分析 …………………...……………. 22
3-3-1. DPPH 自由基清除能力測定 …………………….... 22
3-3-2. 清除超氧陰離子能力測定 ……………………….... 22
3-3-3. 螯合亞鐵離子能力測定 ………………………….... 23
四、細胞實驗 (In vitro) ………………………………………...…… 23
4-1. 細胞培養 ……………………………………………………... 23
4-2. 細胞保存 …………………………………………………….. 24
4-3. 細胞毒性試驗 ……………………………………………….. 24
4-4. 肥大細胞脫顆粒測定 ……………………………………..… 24
4-5. 酵素連結免疫吸附分析法 ………………………………..… 24
4-6. 一氧化氮 (NO) 濃度分析 …………………………………. 25
五、動物實驗 (In vivo) …………………………………………...… 25
5-1. 異位性皮膚炎小鼠動物模式 ……………………………….. 25
5-2. 皮膚炎症狀評估 …………………………………………..… 26
5-3. 石蠟切片 …………………………………………………..… 26
5-3-1. 蘇木素-伊紅染色 ………………………………….. 26
5-3-2. 甲苯胺藍染色 ………………………………...…….. 26
5-4. 酵素連結免疫吸附分析法 …………………………….…….. 26
5-5. 血液分析 ……………………………………………………... 27
5-6. 統計分析 ………………………………………………….….. 27
伍、結果 …………………………………………………………….… 28
一、蛹蟲草菌絲體、子實體萃取物篩選 …………………………... 28
1-1. 蛹蟲草萃取物回收率與成份分析 ………………………...… 28
二、蛹蟲草萃取物之抗氧化能力分析 …………………………….... 28
三、蛹蟲草萃取物對於細胞實驗之影響 …………………………… 28
3-1. 蛹蟲草萃取物對於 P815 老鼠肥大細胞之效果 …………... 29
3-1-1. 細胞毒性測試 ………………………...…………….. 29
3-1-2. Cordyceps militaris 減少 P815 脫顆粒之效果 .. 29
3-1-3. 蛹蟲草萃取物對酵素連結免疫吸附分析法 …….… 29
3-2. 蛹蟲草萃取物對於 RAW 264.7 老鼠巨噬細胞之效果 …... 30
3-2-1. 細胞毒性測試 ……………………………………..... 30
3-2-2.蛹蟲草萃取物對於 RAW264.7 產生一氧化氮 (NO) 之影響 ………………………………………………………… 31
四、蛹蟲草萃取物對於動物實驗之影響 …………………………... 31
4-1. 小鼠皮膚損傷評分及體重 …………………………………... 32
4-2. 小鼠脾臟及淋巴結重量 ……………………………………... 32
4-3. 皮膚組織切片 ……………………………………………...… 32
4-4. 酵素連結免疫吸附分析法 …………………………………... 33
4-4-1. 免疫球蛋白E (Immunoglobin E, IgE) ……………. 33
4-4-2. Th2細胞因子 IL-4、IL-10 …………………………. 33
4-4-3. 干擾素-γ (Interferon-γ, IFN-γ) …………………... 33
4-4-4. 腫瘤壞死因子-α (Tumor necrosis factor-α, TNF-α) ……………………………………………………….... 34
陸、討論 ………………........................................................................... 35
一、蛹蟲草萃取物成分與生活活性分析 …………………………… 35
二、蛹蟲草萃取物抑制以 Compound 48/80 誘導之P815脫顆粒效果 ……………………………………………………………………… 35
2-1. Compound 48/80 對於刺激P815脫顆粒作用 ……………... 35
2-2. 蛹蟲草萃減輕 P815 脫顆粒作用 …………………………. 36
三、蛹蟲草萃改善以 DNCB 誘導之異位性皮膚炎小鼠之效果 .. 36
3-1. 皮膚炎狀態評分 ……………………………………………... 36
3-1-1. 馴養適應期 …………………………………………. 36
3-1-2. 預防、治療對於改善異位性皮膚炎症狀評分之情形 36
3-2. 皮膚組織切片 H&E 染色後角質層增厚 ……………..… 36
3-3. 皮膚組織切片 TB 染色後肥大細胞浸潤現象 ………….. 37
3-4. 血清中抗體與細胞因子分析 ………………………………... 38
柒、結論 ………………………………………………………………....39
捌、參考文獻 ………………………………………………………...… 40
玖、圖 ………………………………………………………………...… 46
拾、表 …………………………………………………………………... 65

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