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標題: | 代謝性與阻塞性傷害引起排尿及腎功能失調之機轉探究 The Pathophysiologic Mechanisms of Metabolic and Obstructive Damage Induced Voiding and Renal Dysfunction |
作者: | Shiu-Dong Chung 鍾旭東 |
指導教授: | 余宏政,鄭劍廷 |
關鍵字: | 代謝症候群,輸尿管阻塞,粒線體傷害,致病機轉,排尿障礙, metabolic syndrome,ureteral obstruction,mitochondrial injury,pathomechanism,voiding dysfunction, |
出版年 : | 2013 |
學位: | 博士 |
摘要: | 排尿障礙 (voiding dysfunction) 以及阻塞性尿路病變 (Obstructive uropathy) 都可說是泌尿科最常見的疾病,也是泌尿科相當重視的研究與治療的主題。臨床上,因尿路結石導致尿路阻塞是最常見並容易造成腎臟的傷害甚至需血液透析治療後者則使得病人的生活品質大受影響並限制其社交活動參與。排尿功能異常 (voiding dysfunction) 在過去常被認為只是因為老化、前列腺增生導致之膀胱出口阻塞以及膀胱逼尿肌的收縮力下降所造成的頻尿、急尿、尿失禁、解尿困難、尿流細小及膀胱內餘尿增加,而近年來也有越來越多的臨床及基礎研究的證據認為代謝症候群是排尿功能異常重要的致病因子之一。這兩種疾病的致病機轉被認為是相當複雜的。近年來,由於分子生物學的進步,過去研究已指出輸尿管阻塞 (ureteral obstruction)造成腎臟損害的機轉與氧化壓力及發炎浸潤有關。此外,我們過去的臨床研究也指出糖尿病或是代謝症候群會明顯地惡化排尿功能,然而這部分的分子生物學層次的致病機轉尚不明確。
我的研究首先以高果糖餵食的動物模式探討代謝症候群所造成的膀胱功能障礙與骨盆神經,外括約肌收縮力及膀胱內壁上的神經傳導受體的變化相關性。這部分研究將有助於了解代謝症候群所改變的下泌尿神經環境在排尿功能異常的發生及進展中所扮演的角色,亦可做為日後發展藥物治療的方向之一。另外我的研究將以單側輸尿管阻塞 (unilateral ureteral obstruction, UUO) 的動物模式探討氧化壓力導致腎臟內活性氧化物增加導致細胞凋亡 (apoptosis) ,細胞自噬 (autophagy) 及細胞死亡 (pyroptosis)在阻塞性尿路病變致病機轉上的角色。也試著研究如何利用調節或抑制腎臟內活性氧化物增加在減緩尿路阻塞導致腎臟損傷機轉的研究。 Voiding dysfunction and obstructive uropathy are both the most common diseases in clinical urology. In our field, these two diseases are the important targets for exploring pathologic mechanisms and potential new drug development. In clinical practice, stone disease is the most common etiology for obstructive uropathy, which can result in further kidney damage even irreversible and make patients to receive maintenance hemodialysis. The quality of life among patients with end-stage renal disease at maintenance dialysis therapy will be impaired, and the patients will be limited to social activity. Voiding dysfunction can manifested as urinary frequency, urgency, incontinence, difficult in voiding weak urinary stream and increased post-void residual. In the past, voiding dysfunction was attributed to aging process, prostatic hyperplasia related bladder outlet obstruction and detrusor underactivity. Increasing evidence based on clinical and basic researches suggested that metabolic syndrome can contribute to the bladder dysfunction. In addition, it is reported that oxidative stress and inflammation infiltration are associated with the renal damage by molecular biological studies. Our previous study also found that type 2 diabetes mellitus and metabolic syndrome will further aggravate the bothersome symptoms of voiding dysfunction, however, the underlying pathophysiology remains unclear. The aim of the doctoral thesis is first to investigate the role of metabolic syndrome in the pathophysiology of bladder dysfunction by understanding the disarrangements of pelvic nerves, external sphincter synergy and neurotransmitter receptors by a high-fructose fed animal model. The accomplishment of the studies will provide a comprehensive view of the metabolic syndrome related lower urinary tract neural environment and voiding dysfunction. It also provides the direction of development of new drugs to treat voiding dysfunction in the future. On the other hand, my study will use an animal model of unilateral ureteral obstruction (UUO) to examine the role of oxidative stress induced accumulation of reactive oxygen species (ROS) which result in apoptosis, autophagy and pyroptosis in the pathophysiology of obstructive uropathy and investigate how to modulate or inhibit the increase of ROS to attenuate the renal damage by obstructive uropathy. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61778 |
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顯示於系所單位: | 臨床醫學研究所 |
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