The Pathophysiologic Mechanisms of Metabolic and Obstructive Damage Induced Voiding and Renal Dysfunction

• Main Authors: Shiu-Dong Chung, 鍾旭東
• Other Authors: 余宏政
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/68501253043165003748

博士 === 國立臺灣大學 === 臨床醫學研究所 === 101 === 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.