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研究生:吳怡萱
研究生(外文):WU, YI-HSUAN
論文名稱:自噬作用影響K它命膀胱炎之血管新生作用且改善其膀胱過動症
論文名稱(外文):Autophagy alters bladder angiogenesis and improves bladder hyperactivity in the pathogenesis of ketamine-induced cystitis in a rat model
指導教授:阮雍順阮雍順引用關係
指導教授(外文):JUAN, YUNG-SHUN
口試委員:李偉嘉李永進
口試委員(外文):LEE, WEI-CHIALEE, YUNG‑CHIN
口試日期:2021-06-04
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2021
畢業學年度:109
語文別:英文
論文頁數:66
中文關鍵詞:自噬作用K它命膀胱
外文關鍵詞:AutophagyKetamine-induced cystitis
ORCID或ResearchGate:0000-0003-2366-8268
相關次數:
  • 被引用被引用:0
  • 點閱點閱:13
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  • 下載下載:3
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推論自噬作用可能透過調控血管新生及發炎反應,影響K它命膀胱炎之修復及功能改善。建立K它命膀胱炎的動物疾病模式,分別給予雷帕黴素(Rapamycin)及渥曼青黴素(Wortmannin,磷酸肌醇-3激酶抑制劑),總共將大鼠隨機分做四組: (1)對照組 (2) K它命組 (3) K它命+ 雷帕黴素 (4) K它命 + 渥曼青黴素。檢測大鼠膀胱功能、膀胱逼尿肌收縮活動、自噬小體及自噬溶酶體分佈、白血球總數及白血球分類、自噬作用相關蛋白質表現、血管新生相關生物標記及訊息傳導路徑。實驗結果發現 K它命膀胱炎之大鼠有明顯的逼尿肌過動,呈現間質纖維化及內皮細胞受損,嗜酸性發炎反應,粒線體及胞器腫脹及降解,並抑制血管生成作用及磷酸化蛋白質激酶。雷帕黴素治療會抑制血管生成,移除K它命代謝物,減緩嗜酸性發炎反應,減輕膀胱過動,改善膀胱功能; 渥曼青黴素治療會減緩嗜鹼性發炎反應,透過增加微血管密度及血管內皮生長因子表現改善膀胱血管生成作用。推論自噬作用改善K它命膀胱炎的膀胱功能可能是透過調節發炎反應及血管生成作用。
Background: The present study attempted to elucidate whether autophagy alters bladder angiogenesis, decreases inflammatory response and ameliorates bladder hyperactivity, influencing bladder function in ketamine-induced cystitis (KIC). Methods: Female Sprague-Dawley (S-D) rats were randomly divided into the control group, the ketamine group, the ketamine + rapamycin group, and the ketamine + wortmannin group. The bladder function, contractile activity of detrusor smooth muscle, distribution of autophagosome and autolysosome, total white blood cells (WBCs) and leukocyte differential counts, the expressions of autophagy-associated protein, angiogenesis markers and signaling pathway molecules involved in KIC were tested, respectively. Results: The data revealed that treatment with ketamine significantly resulted in bladder overactivity, enhanced interstitial fibrosis, impaired endothelium, induced eosinophil-mediated inflammation, swelling and degraded mitochondria and organelles, inhibited angiogenesis and elevated the phosphorylation of Akt. But, treatment with rapamycin caused an inhibitory effect on vascular formation, removed ketamine metabolites, decreased the eosinophil-mediated inflammation and ameliorated bladder hyperactivity, leading to improving bladder function in KIC. However, wortmannin treatment reduced basophil-mediated inflammatory response, improved bladder angiogenesis by increasing capillary density and VEGF expression, to reverse anti-angiogenic effect to repair KIC. Conclusions: These findings suggested that autophagy could modulate inflammatory responses and angiogenesis, which improve bladder function in KIC.
中文摘要 2
Abstract 3
Introduction 4
Materials and methods 8
Animals and ketamine administration 8
Isovolumetric cystometrograms (CMGs) 9
Tracing analysis of voiding behavior by metabolic cage 9
Bladder contractility studies 10
Ketamine metabolites assay in urine and serum 10
Histological study by Masson’s Trichrome Stain 11
Measurement of leukocyte count and blood smear 11
Transmission Electron Microscopy (TEM) 12
Protein isolation and Western blot analysis. 12
Immunofluorence staining, confocal microscopy, and automated computer-based image quantification for the location of protein expression 14
Statistical analysis 15
Results 16
Discussion 29
Conclusions 35
Figures and Tables 36
Abbreviation 56
Reference 58

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