臺灣博碩士論文加值系統

慢性傷口癒合過程中發炎反應會較普通傷口癒合嚴重，慢性傷口上的細胞分裂以及生長因子減少，導致傷口一直沒辦法完全癒合，會導致增生期以及重塑期時間增長，增加患者傷口感染的風險，會帶給患者很大的困擾，且現今在手術後常會給予消炎藥，然而消炎藥常會導致頭暈、嗜睡以及腸胃不適等副作用，因此本研究主要探討天然萃取物能否取代消炎藥。裙帶菜水萃物由多種醣類組成，目前已有研究顯示具有多種生理活性和對健康的益處，包含：抗氧化、免疫調節等；鱸魚精富含胺基酸以及膠原蛋白，已有許多研究指出具有多種生理活性和對健康的益處，包含：抗氧化、抗菌以及抗疲勞等作用；淡菜精富含胺基酸、礦物質以及維生素，已有許多研究表明具有多種生理活性和對健康的益處，包含：抗氧化、抗發炎、抗關節炎和保護胃的特性，然而雖然淡菜的營養成分不亞於鱸魚，但卻沒人探討其對於傷口癒合之功效。因此本研究的主旨為探討鱸魚精、淡菜精與裙帶菜水萃物能否藉由鱸魚精、淡菜精與裙帶菜水萃物中多醣降低發炎反應鱸魚精與淡菜精中胺基酸增進營養補充協同改善傷口癒合，透過細胞實驗，使用 MTS assay 觀察鱸魚精、淡菜精與裙帶菜水萃物對小鼠纖維母細胞 L929 是否有毒殺性且是否具有促生長反應，再透過體外傷口划痕實驗模擬體內受傷狀況，觀察鱸魚精、淡菜精與裙帶菜水萃物促進傷口遷移之作用，以及抽取體外傷口划痕後 L929 之 RNA ，經由 qPCR 測定鱸魚精、淡菜精以及裙帶菜水萃物是否可促進細胞中生長因子以及膠原蛋白之產生，最後利用脂多醣 (LPS) 誘導之小鼠巨噬細胞 RAW 264.7 模擬體內發炎狀況，觀察鱸魚精、淡菜精以及裙帶菜水萃物抗發炎之作用，結果顯示鱸魚精、淡菜精以及裙帶菜水萃物對 L929 沒有毒性且可促進細胞生長，更可以藉由促進生長因子以及膠原蛋白，加速細胞遷移以完成傷口癒合，鱸魚精、淡菜精以及裙帶菜水萃物皆可抑制巨噬細胞 NO 的產生，抑制發炎反應；在動物實驗方面，利用手術將小鼠背部生成 36 mm2 的傷口，觀察 12 天內小鼠的傷口癒合效果，結果顯示，觀察到口服給予樣品，在鱸魚精以及淡菜精組可最快促進小鼠傷口癒合率，其次是混合給予組以及裙帶菜水萃物組，且透過染色以及 ELISA 可發現鱸魚精、淡菜精以及裙帶菜水萃物藉由促進血管生成因子 (VEGF) 和膠原蛋白生成以及降低促炎生長因子產生以抑制發炎反應，以此來促進傷口癒合，綜上所述，管餵鱸魚精、淡菜精以及裙帶菜水萃物皆可改善傷口癒合能力，因此未來鱸魚精與淡菜精可協同裙帶菜水萃物成為術後傷口癒合之新型營養補品之潛力。

During the healing process of chronic wounds, due to reduced cell division and growth factors, leading to a prolonged healing process. There is an increased risk of wound infection. Anti-inflammatory drugs are often used after surgery. However, these drugs cause several side effects such as dizziness and gastrointestinal discomfort. Therefore, this study aims to explore whether natural extracts can replace these drugs. First natural extract is Undaria pinnatifida water extract (UPw), which has been studied for its antioxidative and immune-regulatory properties. Another extract being studied is bass essence (BE), rich in amino acids and collagen, and known for its antioxidative and antibacterial effects. The third is mussel essence (ME), containing amino acids and collagen, and known for antioxidative, anti-inflammatory, and anti-arthritis. Therefore, the main objective of this research is to investigate whether BE, ME, and UPw can improve wound healing by reducing inflammation through the polysaccharides and enhancing nutritional supplementation through the amino acids. The study involves cell experiments using MTS assay to observe the effects of BE, ME, and UPw on mouse fibroblast cells (L929), assessing cytotoxicity and growth-promoting effects. Additionally, an in vitro wound scratch experiment is to observe the wound healing promotion effects of BE, ME, and UPw. RNA is extracted from the scratched L929 to measure the production of growth factors and collagen by qPCR, to determine whether samples can promote their production. Furthermore, LPS-induced mouse macrophages (RAW 264.7) are used to measure the anti-inflammatory effects of BE, ME, and UPw. The results show that BE, ME and UPw are non-toxic to L929 and can promote cell growth. They also accelerate cell migration by stimulating the production of growth factors and collagen, thereby facilitating wound healing. BE, ME and UPw can also inhibit the production of nitric oxide in RAW, demonstrating their anti-inflammatory properties. In animal experiments, mice with 36 mm2 wounds on their back are orally administered with the samples and observed for 12 days. The results showed that most rapidly promote wound healing rate in the group treated with BE and ME, followed by the group treated with a combination and the group treated with UPw. Staining and ELISA analysis reveal that BE, ME and UPw enhance the production of vascular endothelial growth factor and collagen, while reducing pro-inflammatory cytokines, thereby suppressing inflammation and facilitating wound healing. In summary, BE, ME and UPw can enhance wound healing capabilities. Therefore, the combined use of BE and ME with UPw holds potential as a novel nutritional supplement for postoperative wound healing.

摘要 ..………………………………………………………………………………… I
Abstract …………………………………………………………………………...…. II
目錄 ………………………………………………………….…………………….. III
圖目錄 …….…………………………………………………….………………..... VI
表目錄 ……………………………………………………………………………. VIII
壹、前言
貳、文獻回顧
一、 皮膚構造及功能
1. 表皮 (Epidermis)
1-1 角質層 (Stratum corneum) ……………………………………… 2
1-2 透明層 (Stratum lucidum) ………………………………………. 2
1-3 顆粒層 (Stratum granulosum) …………………………………... 3
1-4 棘狀層 (Stratum spinosum) ……………………………………... 3
1-5 基底層 (Stratum basale) ………………………………………… 3
2. 真皮層 (Dermis)
2-1 乳頭層 (Papillary layer) 4
2-2 網狀層 (Reticular layer) 4
3. 皮下組織 (Subcutaneous tissue) …..………………………………………………… 4
二、 傷口癒合
1. 止血期……………………………………………………………...… 5
2. 炎症期………………………………………………………………... 5
3. 增生期………………………………………………………………... 5
4. 重塑期………………………………………………………………... 6
5. 生長因子於傷口癒合之作用 ……………………………………….. 6
6. 游離胺基酸於傷口癒合之作用 …………………………………….. 6
7. 慢性傷口癒合 ……………………………………………………….. 7
三、 海藻
1. 褐藻 (Chlorophyta)…………………………….……………………... 7
1-1. 裙帶菜 (Undaria pinnatifida) …………………….…………… 8
2. 裙帶菜水萃物 (Undaria pinnatifida water extract, UPw) …………... 8
四、 鱸魚
1. 鱸魚精 …………………………………………………………….… 8
五、 淡菜
1. 淡菜精 ……………………………………………………………...… 9
參、實驗設計流程
一、 鱸魚精特性分析……………………………………………………… 11
二、 細胞實驗……………………………………………………………… 11
三、 動物實驗……………………………………………………………… 12
肆、實驗材料與方法
一、 實驗材料
1. 樣品原料 ……………...………………………………………….…. 13
2. 抗氧化試驗………………………………………………………….. 13
3. 細胞株……………………………………………………………….. 13
4. 細胞培養之培養基………………………………………………….. 13
5. 細胞存活率試劑………………………………………….…………. 14
6. 體外傷口癒合實驗……………………………………….…………. 14
7. 一氧化氮 (NO) 生成抑制率試驗………………..……….…………. 14
8. 實驗動物………………………………………………….…………. 14
9. 組織切片………………………………………………….…………. 14
10. 酵素連結免疫吸附分析法……………………………….…………. 15
11. RNA 萃取套組………………………………………………………. 15
12. 反轉錄反應試劑……………………………………….……………. 15
13. 即時定量聚合酶連鎖反應試劑 (Real-time PCR) …..….………….. 15
二、 儀器設備………………………………….……………………………… 16
三、 實驗方法
1. 實驗樣品製備 ……………………………………….………………. 16
1-1.熱水萃取法 ……………………………………………………… 17
1-2.鱸魚精以及淡菜精萃取法 ……………………………………… 17
2. 樣品特性分析…………………..……………………………………. 17
2-1.抗氧化能力試驗…………………..……………………………... 17
2-1-1.清除DPPH (α,α-diphenyl-β-picryhydrazyl) 自由基能力測定
2-1-2.清除超氧陰離子能力測定
2-1-3.螯合亞鐵離子能力測定…………………..…………………... 18
3. 細胞實驗 (In vitro)
3-1.小鼠纖維母細胞 (L929) 培養 …..……………………………... 18
3-2.小鼠巨噬細胞 (RAW 264.7) 培養 ……………….……………... 18
3-3.細胞保存…………………..………………………….……….…. 19
3-4.細胞活化…………………..………………………….………..… 19
3-5.纖維母細胞毒性測試 (Cytotoxicity test) ………………….…… 19
3-6.酵素連結免疫吸附分析法 (Enzyme-linked immunoadsorbent assay, ELISA) ………………….…………………………….……………... 19
3-7.體外划痕實驗 (Scratch wound healing assay) ……….…………. 20
3-8.分析組織中細胞激素之 mRNA 表現量
3-8-1. 抽取細胞 total RNA ………………………………………….. 20
3-8-2. 反轉錄反應 (Reverse transcription, RT) ……………………... 20
3-8-3. 即時聚合酶連鎖反應 (Real-time polymerase chain reaction) . 21
3-9. 一氧化氮試驗濃度分析 (NO assay) …………………..………. 21
4. 動物實驗 (In vivo)
4-1. 手術製造小鼠傷口模式………………….….……...….……….. 21
4-1-1.皮膚傷口症狀評估………………….………………………… 21
4-2.口服鱸魚精、淡菜精以及裙帶菜水萃物促進傷口癒合小鼠之效果………………….………………………………………………..... 22
4-3.組織病理石蠟切片………………….…………………………… 22
4-3-1.蘇木素-伊紅染色 (Hematoxylin and eosin stain, H&E stain) ... 22
4-3-2. Masson三色染色 (Masson's Trichrome stain) …………….… 22
4-3-3.免疫組織化學染色法 (Immune histo chemistry, IHC) ………. 23
4-4. 血液分析………………….…………………………………...… 23
5. 統計分析……………………………………………………………... 23
伍、結果……….…………………………………………………………………… 24
陸、討論 ...…………………………………………………………………………. 29
柒、結論 ...………………………………………….……………………………… 35
捌、參考文獻………………………………………….…………………………… 36
玖、圖表 …...……………………………………………...……………………….. 44

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