臺灣博碩士論文加值系統

糖尿病為現代常見的慢性疾病，會使血液中葡萄糖含量過高，可藉由飲食調控。靈芝屬於一種白腐真菌，富含靈芝多醣、蛋白多醣及三萜類，具有降血糖與抗肥胖活性。當靈芝與其他微生物共培養，可因營養源競爭與代謝物刺激有效提升靈芝菌絲體內三萜類含量及靈芝胞外多醣產量。本研究旨探討低溫及酵母菌共培養對靈芝生長與活性物質產生的影響，並以 FL83B 細胞膜式探討其對降血糖活性之影響。靈芝單株或與酵母菌共培養在 20℃ 所得菌絲球直徑、菌絲體乾重、胞外多醣含量及菌絲體三萜類含量皆顯著大於 30℃ 組別所得。靈芝與酵母菌共培養可增加胞外多醣與菌絲體三萜類含量。20℃ 共培養所得胞外多醣及菌絲體三萜類含量分別為 1.43 ± 0.05 g/L 與 23.61 ± 2.14 mg/g，顯著高於 20℃ 靈芝單株所得之 1.32 ± 0.01 g/L 與 20.7 ± 1.03 mg/g。靈芝與酵母菌共培養之凍乾發酵粉末分別進行沸水萃取伴隨乙醇沉澱 (熱水萃) 與氨水萃取 (氨水萃)。同樣溫度下，熱水萃所得之萃取率雖於氨水萃，然其總碳水化合物含量顯著高於氨水萃，且其 β -葡聚醣含量顯著較高。熱水萃取物主要由醣類與蛋白質構成，氨水萃取物由蛋白質構成。共培養兩種萃取物在濃度 100-500 μg/mL 下不影響 FL83B 細胞存活率。共培養所得兩種萃取物均顯著提高 20 ng/mL Tumor Necrosis Factor-alpha (TNF-α) 所導致胰島素阻抗細胞之葡萄糖吸收率，由 67% 提高至 80%以上，在胰島素存在下，樣品可進一步提高至正常細胞相對葡萄糖攝取量。共培養兩種萃取物在濃度 100-500 μg/mL 20℃ 熱水萃取物、20℃ 氨水萃取物、30℃ 氨水萃取物及 100 和 200 μg/mL 30℃ 熱水萃取物可顯著提升肝醣含量。其中 20℃ 共培養水萃取物在 300 μg/mL 下肝醣含量可增加到 3.17 μg/mL。若含有胰島素下，所有萃取物在 100-500 μg/mL 肝醣含量皆與正常細胞肝醣含量無顯著差異。綜上所述，20℃ 單株靈芝可提升其菌絲體乾重、胞外多醣含量及菌絲體三萜類含量，而與酵母菌共培養可更進一步提升胞外多醣與三萜類含量。兩種溫度共培養發酵萃取凍乾物具增加胰島素阻抗細胞之相對葡萄糖吸收與肝醣含量活性，未來可進一步探討兩種共發酵萃取物對降血糖活性機制相關基因與蛋白質表現量之影響。

Diabetes mellitus, a prevalent chronic disease in modern society, leads to elevated blood glucose levels, which can be managed through dietary regulation. Ganoderma lucidum, a type of white-rot fungus, is rich in polysaccharides, proteoglycans, and triterpenoids, and exhibits hypoglycemic and anti-obesity activities. Co-cultivation of Ganoderma lucidum with other microorganisms can effectively enhance the triterpenoid content in the mycelium and the yield of extracellular polysaccharides due to nutrient competition and metabolite stimulation. This study aims to investigate the effects of low temperature and co-cultivation with yeast on the growth and production of bioactive substances in Ganoderma lucidum, and evaluate its hypoglycemic activity using FL83B cell models. The diameter of mycelial pellets, dry weight of mycelium, extracellular polysaccharide content, and triterpenoid content in the mycelium obtained from co-cultivation at 20°C were significantly higher than those obtained at 30°C. Co-cultivation of Ganoderma lucidum with yeast increased the content of extracellular polysaccharides and triterpenoids in the mycelium. The extracellular polysaccharide and triterpenoid content from co-cultivation at 20°C were 1.43 ± 0.05 g/L and 23.61 ± 2.14 mg/g, respectively, significantly higher than those from single cultivation at 20°C (1.32 ± 0.01 g/L and 20.7 ± 1.03 mg/g). The lyophilized fermentation powders from co-cultivation were subjected to boil water extraction along with ethanol precipitation (boil water extract) and ammonia extraction (ammonia extract). At the same temperature, the extraction yield of boil water extract was higher than that of ammonia extract, with significantly higher total carbohydrate content and β-glucan content in the boil water extract. The boil water extract was primarily composed of carbohydrates and proteins, while the ammonia extract consisted of proteins. The co-cultivation extracts did not affect the viability of FL83B cells at concentrations of 100-500 μg/mL. Both extracts significantly increased the glucose uptake rate in insulin-resistant cells induced by 20 ng/mL Tumor Necrosis Factor-alpha (TNF-α), from 67% to over 80%. In the presence of insulin, the samples further enhanced glucose uptake to normal cell levels. The extracts from co-cultivation at concentrations of 100-500 μg/mL (20°C boil water extract, 20°C ammonia extract, 30°C ammonia extract) and at 100 and 200 μg/mL (20°C boil water extract) significantly increased glycogen content. The 20°C co-cultivation boil water extract at 300 μg/mL increased glycogen content to 3.17 μg/mL. If insulin is present, the glycogen content of all extracts at concentrations of 100-500 μg/mL does not show any significant difference compared to the glycogen content of normal cells. In summary, cultivating Ganoderma lucidum at 20°C enhances the dry weight of its mycelium, the extracellular polysaccharide content, and the triterpenoid content of the mycelium. Co-culturing with yeast further increases the extracellular polysaccharide and triterpenoid content. Extracts from the lyophilized co-cultivation fermentation at both temperatures exhibit enhanced relative glucose uptake and glycogen content in insulin-resistant cells. Future studies can further investigate the effects of these co-fermentation extracts on the expression of genes and proteins related to hypoglycemic mechanism.

目錄
摘要 IV
Abstract VI
目錄 VIII
圖目錄 XI
表目錄 XII
名詞縮寫表 XIII
壹、前言 1
貳、文獻整理 2
一、糖尿病 2
1. 糖尿病定義與診斷標準 2
2. 糖尿病分類 2
2.1 第一型糖尿病 2
2.2 第二型糖尿病 3
2.3 妊娠型糖尿病 3
2.4 其他型糖尿病 3
二、胰島素 4
1. 胰島素簡介 4
2. 胰島素訊息傳遞路徑及其分子機制 4
3. 胰島素阻抗 (Insulin resistance) 5
3.1 定義與病因 5
3.2 誘發胰島素阻抗之肝臟細胞模式 5
三、靈芝 6
1. 靈芝簡介 6
2. 靈芝培養 7
2.1 培養方式 7
2.2 溫度 8
3. 靈芝活性物質 8
3.1 靈芝多醣 8
3.2 靈芝三萜類 9
4. 靈芝生理活性 10
4.1 降血脂及抗肥胖作用 10
4.2 降血糖與降血壓作用 11
四、酵母菌 12
1. 酵母菌簡介 12
2. 酵母菌降血糖活性 12
五、共培養 13
六、FL83B 細胞 14
參、實驗設計 15
肆、實驗材料與方法 16
一、實驗材料 16
1. 材料 16
2. 實驗菌株與細胞株 16
3. 化學藥品 16
4. 培養基 17
二、儀器設備 18
三、實驗方法 19
1. 菌株保存與活化 19
1.1 菌株保存 19
1.2 菌株的活化與繼代 19
2. 培養溫度對單株靈芝與酵母菌生長與活性物質之影響 20
3. 靈芝與酵母菌共培養對活性物質之影響 20
4. 發酵液分析 21
4.1 單株或共培養發酵液凍乾粉末之製備 21
4.2 靈芝發酵菌絲體之製備與分析 21
4.3 靈芝菌絲球大小測定 21
4.4 靈芝發酵菌絲體內三萜類之製備與分析 21
4.5 靈芝發酵液胞外多醣體之製備與分析 22
4.6 酵母菌平板計數分析 22
4.7 酵母菌體 β-葡聚醣含量分析 22
4.8 pH 值測定 24
4.9 還原糖含量測定 24
4.10 總胜肽含量測定 25
4.11 總糖含量測定 25
4.12 蛋白質含量測定 26
5. 發酵液之萃取物製備 26
5.1 100oC 熱水萃取與乙醇沉澱 26
5.2 氨水萃取 27
6. 發酵萃取物樣品對 FL83B 細胞進行葡萄糖吸收與肝醣含量的影響 27
6.1 FL83B 細胞培養與繼代 27
6.2 樣品對 FL83B 細胞株存活率測試 28
6.3 誘導 FL83B 細胞產生胰島素阻抗並測定葡萄糖吸收率 28
6.4 誘導 FL83B 細胞產生胰島素阻抗並測定細胞內肝醣含量 29
7. 統計分析 29
伍、結果與討論 30
一、溫度對單株靈芝生長的影響 30
二、溫度對單株酵母菌單株生長的影響 31
三、共培養對活性物質之影響 32
四、兩種萃取方法對靈芝與酵母菌共培養發酵液活性物質之影響 34
五、共培養發酵液凍乾萃取物對細胞存活率影響 35
六、共培養發酵液凍乾萃取物對細胞葡萄糖吸收影響 36
七、共培養發酵液凍乾萃取物對細胞肝醣含量影響 38
陸、結論 40
柒、參考文獻 41
捌、圖表 54

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