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研究生: 蔡文興
Tsai, Wen-Hsin
論文名稱: 傳統中醫藥對於發炎性疾病的治療潛力
Therapeutic Potential of Traditional Chinese Medicine on Inflammatory Diseases
指導教授: 吳忠信
Wu, Chung-Hsin
鄭劍廷
Chen, Chiang-Ting
學位類別: 博士
Doctor
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2016
畢業學年度: 104
語文別: 英文
論文頁數: 84
中文關鍵詞: 細胞凋亡細胞自噬發炎氧化壓力傳統中醫學膀胱過動症P物質八味地黃丸茶氨酸
英文關鍵詞: Apoptosis, Autophagy, Inflammation, Oxidative stress, Traditional Chinese Medicine, Overactive bladder, Substance P, BWDHW, Theanine
DOI URL: https://doi.org/10.6345/NTNU202204403
論文種類: 學術論文
相關次數: 點閱:182下載:35
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  • 氧化壓力的增加,誘發多個組織/器官的發炎,導致細胞死亡和長期傷害。傳統的中醫學(TCM)具有抗氧化,抗發炎,抗凋亡和自噬調控功能已被廣泛地用在現代醫學中的預防或治療策略。氧化壓力和發炎已經被廣泛報導有關於臨床上所見P物質介導的神經源性膀胱過動。
    為了改善膀胱過動症,我們探討潛在的藥物和神經源性膀胱機制。 P物質(SP)會藉由興奮膀胱的感覺傳入神經和細胞間粘附分子-1(ICAM-1)介導白血球粘附和活性氧族(ROS)產物的增加引起的膀胱過動。八味地黃丸(BWDHW)是一種傳統的中草藥複方,一直使用來治療罹患下尿路症狀的患者,但作用機轉並不清楚。我們在本研究探討其中的活性成分及BWDHW對於SP誘發膀胱活動過度的影響。結果顯示,BWDHW是經由loganin抑制SP /神經激肽-1(NK-1)受體信號傳導,降低NF-κB/ ICAM-1介導白血球粘附和浸潤和ROS水平,因而改善膀胱過動症狀。
    我們也探討L-茶氨酸對於P物質誘導的促炎信號PKC / ERK / NF-κB/ ICAM-1 / IL-33,白血球浸潤和粘附,活性氧(ROS)產物,自噬和凋亡對膀胱過動的療效。總之,口服L-茶氨酸確定能藉由抑制促炎信號,氧化壓力,膀胱神經活性,細胞凋亡和自噬,改善P物質誘導的膀胱過動。

    Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to substance P–mediated neurogenic hyperactive bladder based on clinical findings.
    To improve hyperactive bladder, we explored potential drugs and mechanism on neurogenic bladder. Substance P (SP) induced hyperactive bladder via the enhancement of bladder afferent signaling and intercellular adhesion molecule-1 (ICAM-1) mediated leukocyte adhesion and ROS production. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese herbal mixture, has been used to treat lower urinary tract symptoms in patients by undefined mechanisms. We investigated the active components and effects of BWDHW on SP-induced bladder hyperactivity. Our results indicate that BWDHW via loganin improves bladder hyperactivity via inhibiting SP/neurokinin-1 receptor signaling and depressing NF-κB/ICAM-1 mediated leukocyte adhesion and infiltration and ROS levels.
    We explored the effect of L-theanine treatment on SP-induced proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, leukocyte infiltration and adhesion, ROS production, autophagy and apoptosis in the bladder. In summary, oral intake L-theanine ameliorates substance P-induced bladder hyperactivity via the inhibition of proinflammatory signaling, oxidative stress, exaggerated bladder nerve activity, apoptosis and autophagy.

    TABLE OF CONTENTS I LIST OF FIGURES II 中文摘要 V ABSTRACT VI CHAPTER 1 INTRODUCTION 1 CHAPTER 2 RESEARCH AIMS 9 CHAPTER 3 Ba-Wei-Di-Huang-Wan through its Active Ingredient Loganin Counteracts Substance P-Enhanced NF-κB/ICAM-1 Signaling in Rats with Bladder Hyperactivity 11 1. MATERIALS AND METHODS 12 Chromatographic fingerprint analysis for the BWDHW 12 Animals 12 Treatment with BWDHW 14 Hemodynamics and cystometric parameters 14 Pelvic afferent nerve activity recording 15 In vitro and in vivo chemiluminescence recording for ROS activity 16 Pathology and immunohistochemistry 17 Real-time Quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) 17 Western blotting 18 Statistical analysis 19 2. RESULTS 20 Antioxidant activity of BWDHW on H2O2 and HOCl 20 BWDHW depresses SP-induced bladder hyperactivity 20 BWDHW inhibits SP-enhanced voiding frequency and PANA activation 20 BWDHW decreased SP-enhanced inflammatory leukocytes and ROS in the bladder 21 BWDHW decreased SP-enhanced ICAM-1 expression 22 3. DISCUSSION 38 CHAPTER 4 L-Theanine Inhibits Proinflammatory PKC/ERK/ICAM-1/IL-33 Signaling, Apoptosis and Autophagy Formation in Substance P-induced Hyperactive Bladder in Rats 42 1. MATERIALS AND METHODS 43 Animals 43 Treatment with L-theanine 44 Hemodynamics and cystometric parameters 44 Pelvic afferent nerve activity recording 45 In vitro and in vivo chemiluminescence recording for ROS activity 46 Pathology and immunohistochemistry 47 NF-κB p65 Assay 47 Western blotting 48 Statistical analysis 49 2. RESULTS Antioxidant activity of L-theanine on H2O2 and HOCl 50 L-theanine depresses SP-induced bladder overactivity 50 L-theanine inhibits SP-enhanced voiding frequency and PANA activation 51 L-theanine decreased SP-enhanced PKC/ERK/IL-33, LC3 II, cleaved Caspase 3 and PARP expression 52 3. DISCUSSION 68 CHAPTER 5 CONCLUSIONS 73 REFERENCES 76 ABBREVIATIONS AND ACRONYMS 83 APPENDIX 1: CV of Wen-Hsin Tsai i APPENDIX 2: Copy of Published Sci Papers ii

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