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系統識別號 U0007-0108201110275000
論文名稱(中文) Dexmedetomidine 對受到缺血傷害的血腦屏障之作用
論文名稱(英文) Effects of Dexmedetomidine on Ischemia Injured Blood Brain Barrier—A Cerebral Endothelial Cell Model
校院名稱 臺北醫學大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Graduate Institute of Clinical Medicine
學年度 99
學期 2
出版年 100
研究生(中文) 劉孟琦
研究生(英文) Meng-Chi Liu
學號 M118098003
學位類別 碩士
語文別 英文
口試日期 2011-07-07
論文頁數 51頁
口試委員 指導教授-吳志雄
共同指導教授-陳瑞明
委員-黃俊仁
委員-程毅君
委員-翁芸芳
中文關鍵字 缺血  血腦屏障 
英文關鍵字 dexmedetomidine  ischemia  blood-brain barrier  cerebral endothelium 
學科別分類
中文摘要 簡介:α2腎上腺受體促進劑已廣泛地使用於止痛、抗焦慮、鎮定、交感神經抑制、與麻醉輔助藥物,而目前已由實驗室證實它們亦有神經保護的潛在功能,但作用機轉並未明確。腎上腺受體形成內生性交感神經激素與其標的細胞之間的媒介,並且分布於全身,擔負著許多生理及藥理功能。它們屬於G蛋白質結合家族的跨細胞膜受體,存在於中樞與周邊神經系統、節前與節後交感神經。受體被刺激後會使G蛋白質結合並抑制adenylyl cyclase 及 phospholipase C的活性,接著抑制鈣離子流入細胞、促進鉀離子通道活性,最後造成細胞膜電位降低,偏向極化。假說:Dexmedetomidine 藉由α2腎上腺受體達到對缺血性傷害的腦血管內皮細胞的保護作用。研究目標:觀察dexmedetomidine 對缺血性傷害的腦血管內皮細胞有無保護作用,以及對缺血性傷害的腦血管內皮細胞生理功能之影響。結果:MTT試驗中,dexmedetomidine 能改善缺血性傷害腦血管內皮細胞生存力,在生理功能方面,dexmedetomidine 使缺血性傷害的腦血管內皮電阻及通透性降低的程度減少。結論:Dexmedetomidine 能改善因缺血性傷害的腦血管內皮細胞存活力及生理功能。
英文摘要 Introduction: α2-adrenoceptor agonists are widely used for analgesia, antianxiety, sedation, sympatholysis and as anaesthetic-adjuncts. Their potential use as neuroprotectants has so far been confined to laboratory experiments yet the exact neuroprotective mechanisms remain uncertain. Adrenoreceptors form the interface between the endogenous catecholamines and their target cells that are distributed ubiquitously in the body, mediating the biological effects of many pharmaceutical agents. They are members of the G-protein-coupled family of transmembranous receptors, in the central and peripheral nervous system at both pre- and post-synaptic autonomic ganglia. Activation of these receptors results in G-protein coupling with the inhibition of both adenylyl cyclase and phospholipase C activity. Then the inhibition of calcium ion entry and activation of outward-opening potassium ion channels result in membrane hyperpolarization. α2-adrenoceptor agonists possesses neuroprotective properties in various experimental models of cerebral ischemia, and attenuated hypoxic–ischemic brain injury in developing brains, highly susceptible to neuronal damage. Hypothesis: Dexmedetomidine has neuroprotective effect on hypoxic-ischemic cerebral endothelial cells via the α2A-adrenoceptor. Aim of investigation: To observe protective effects and physiological alterations of dexmedetomidine on hypoxic-ischemic cerebral endothelium. Results: MTT assay revealed improved viability of cerebral endothelial cells (CECs) in co-treated and post-treat group under ischemia exposure. Confocal microscopy and Western blot confirmed that α2A-adrenoceptor existed on CECs. Trans-epithelial electrical resistance (TEER) and permeability were both decreased under ischemia exposure. Conclusion: Cerebral endothelial cells had stronger tolerance to OGD injury, yet physiological function had been interfered much earlier before cell death occurred.
論文目次 Abstract in Chinese 5
Abstract in English 6
Introduction 7
Molecular pharmacology of dexmedetomidine 7
Clinical application 8
Neuroprotection, a shedding light 11
The blood-brain barrier (BBB) 13
Hypothesis 14
Aim of investigations 14
Material and Methods 15
Experiment designs 15
Drugs and solutions 16
Preparation of cells 17
Pathological stimulation 17
Assessment of cellular damage 18
Assessment of physiological functions 20
Assessment of target receptor 21
Data analysis 22
Results 23
Discussion 25
Conclusion and Perspective 28
References 29
Tables and Figures 38
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