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研究生: 黃淨盈
Huang, Jing-Ying
論文名稱: 以糖尿病大鼠模式探討負離子與後生元對皮膚傷口癒合之效應
Investigating the Effects of Negative Ions and Postbiotics on Skin Wound Healing in a Diabetic Rat Model.
指導教授: 鄭劍廷
Chien, Chiang-Ting
口試委員: 鄭劍廷
Chien, Chiang-Ting
陳冬生
Chen, Tung-Sheng
徐世平
Hsu, Shih-Ping
口試日期: 2024/07/30
學位類別: 碩士
Master
系所名稱: 生技醫藥產業碩士學位學程
Graduate Program of Biotechnology and Pharmaceutical Industries
論文出版年: 2024
畢業學年度: 112
語文別: 中文
論文頁數: 69
中文關鍵詞: 傷口癒合急性傷口M1巨噬細胞TNF-αIL-1βMMP-9糖尿病傷口負離子後生元
英文關鍵詞: wound healing, acute wounds, M1 macrophages, TNF-α, IL-1β, MMP-9, diabetic wounds, negative ions, postbiotics
研究方法: 實驗設計法
DOI URL: http://doi.org/10.6345/NTNU202401608
論文種類: 學術論文
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  • 傷口癒合是分子秩序井然的協同過程,過程中任一環節調控異常便可能導致傷口癒合不良。傷口癒合不良原因之一為發炎因子TNF-α與IL-1β顯著升高,引起M1型巨噬細胞過度活化,進而誘發MMP-9過度分泌,破壞傷口處的細胞外基質,以至於傷口的重建和癒合被干擾。同時,M1巨噬細胞透過自泌TNF-α與IL-1β自我刺激,保持在促發炎態,形成一發炎正回饋,導致傷口持續發炎延長癒合時間。在糖尿病患者中,傷口癒合困難更為明顯,因高血糖環境使發炎因子濃度居高不下,持續的發炎反應導致傷口癒合被顯著延遲。過去負離子被提出具有促進血液循環、改善氧化壓力的效用;後生元也曾被提出對於皮膚慢性傷口有所幫助,因此,基於上述背景,高表現量的發炎症因子、MMP-9與M1型巨噬細胞的過度活化,是傷口癒合不佳的主因之一,是故,阻斷M1型巨噬細胞引起的發炎回饋循環是改善傷口癒合的關鍵,在其中的負離子與後生元角色值得探究。
    本研究旨在探討負離子與後生元對糖尿病傷口癒合的影響,研究採用鏈脲佐菌素(STZ)誘導糖尿病大鼠模型,建立背部全皮層傷口,實驗分作對照組、糖尿病組、傷口治療組和糖尿病傷口治療共四組。經負離子、後生元處理組的傷口癒合速度與未治療組相比皆顯著加快,同時,負離子與後生元終止傷口的持續發炎,並促進使傷口處膠原蛋白增生、肉芽組織形成與再上皮化發生,使組織修復和傷口癒合。
    綜上所述,負離子和後生元兩者可以降低氧化壓力、減少發炎反應,甚至可能可以調節M1型巨噬細胞功能,以加速傷口癒合,在改善傷口癒合方面具潛在應用價值,同時提供急性傷口另一新型、有效的治療策略。

    Wound healing is a coordinated process that can be disrupted by regulatory abnor-malities, leading to impaired healing. Elevated inflammatory factors such as TNF-α, IL-1β and hyperactivate M1 macrophages, causing excessive secretion of MMP-9, which de-grades the extracellular matrix and disrupts wound reconstruction. M1 macrophages self-stimulate through autocrine of TNF-α and IL-1β, creating a positive feedback loop of inflammation that prolongs healing. In diabetic patients, high blood sugar exacerbates this issue, keeping inflammatory factor levels high and significantly delaying wound healing.
    Previous studies suggest that negative ions can promote blood circulation and reduce oxidative stress, while postbiotics may aid in chronic skin wounds. This study investi-gated the effects of negative ions and postbiotics on diabetic wound healing using a streptozotocin (STZ)-induced diabetic rat model with full-thickness back wounds. The experiment includes four groups: control, diabetes, wound treatment, and diabetes wound treatment. Treatment with negative ions and postbiotics significantly accelerated wound healing compared to untreated groups. Additionally, these treatments reduced persistent inflammation, promoted collagen proliferation, granulation tissue formation, and re-epithelialization, facilitating tissue repair and wound healing.
    In summary, negative ions and postbiotics can reduce oxidative stress and inflamma-tion, and potentially regulate M1 macrophage function to accelerate wound healing. These findings suggest their potential application in improving wound healing, offering a novel and effective treatment strategy for wound healings.

    謝辭 i 目錄 ii 圖目錄 v 中文摘要 vi Abstract vii 第一章、緒論 1 1.1. 研究背景 1 第二章、文獻回顧 3 2-1. 皮膚構造 3 2-1-1. 表皮層(Epidermal) 3 2-1-2. 真皮層(Dermal) 3 2-1-3. 皮下組織(Hypodermis) 4 2-2. 皮膚傷口癒合的過程 4 2-2-1. 止血期 ( Hemostasis ) 4 2-2-2. 發炎期 (Inflammatory phase) 5 2-2-3. 增生期(Proliferative phase) 6 2-2-4. 重建期(Remodeling phase) 6 2-3. 傷口癒合相關分子 7 2-3-1. 巨噬細胞 7 2-3-2. 腫瘤壞死因子-alpha 8 2-3-3. 白血球介素-1 9 2-3-4. 細胞基質第九金屬蛋白酶 10 2-3-5. 內源性組織金屬蛋白酶抑制因子 11 2-3-6. 傷口癒合不佳分子機制 12 2-4. 糖尿病與傷口癒合 12 2-4-1. 糖尿病 12 2-4-2. 糖尿病傷口癒合不良 13 2-4-3. 糖尿病傷口癒合分子機制變化 14 2-4-4. 常見促進糖尿病傷口癒合之方法 14 2-5. 負離子 15 2-5-1. 負離子產生來源 15 2-5-2. 負離子與健康 15 2-6. 後生元 16 2-6-1. 後生元產生來源 16 2-6-2. 後生元與健康 16 2-7. 研究目的 17 第三章、研究材料與方法 18 3-1. 實驗動物 18 3-2. 大鼠糖尿病模式建立 19 3-3. 背部全皮層傷口模式建立 19 3-3-1. 傷口癒合大小測量 20 3-4. 治療模式 20 3-4-1負離子治療模式 20 3-4-2 後生元治療模式 20 3-5. 生理參數測量 21 3-5-1. 體重測量 21 3-5-2. 血糖測量 21 3-6. 組織病理切片染色分析 21 3-6-1. 蘇木精-伊紅染色( Hematoxylin & Eosin stain, H&E stain ) 21 3-6-2. 馬森三色染色(Masson’s trichrome stain) 22 3-6-3. 天狼星紅染色(Sirius red stain) 22 3-6-4. 羥脯胺酸呈色分析(Hydroxyproline colorimetric assay) 23 3-6-5. 西方墨點法( Western blotting) 23 3-7. 脂質過氧化測定(Lipid peroxidation assay) 24 3-8. 統計分析 24 第四章、實驗結果 26 4-1. 負離子組 26 4-1-1. 負離子清除自由基能力測定 26 4-1-2. 負離子治療脂質過氧化檢測 26 4-1-3. 負離子治療對體重與血糖的影響 26 4-1-4. 負離子治療對皮膚傷口面積的影響 27 4-1-5. 負離子治療造成皮膚組織型態之改變 28 4-1-6. 負離子治療皮膚組織分子改變 29 4-2. 舒洙LACTERA水性創傷敷料組 30 4-2-1. LACTERA清除自由基能力測定 30 4-2-2. LACTERA治療脂質過氧化檢測 30 4-2-3. LACTERA治療對體重與血糖的影響 30 4-2-4. LACTERA治療對皮膚傷口面積的影響 31 4-2-5. LACTERA作為治療皮膚組織型態之影響 32 4-2-6. LACTERA治療皮膚組織分子改變 33 第五章、討論 34 第六章、結論 38 參考文獻 39

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