Yang Zhongguang, Dolber Paul C, Fraser Matthew O
Division of Urology, Department of Surgery, Duke University Medical Center, Veterans Affairs Medical Center, Durham, North Carolina 27710, USA.
J Urol. 2007 Nov;178(5):2213-9. doi: 10.1016/j.juro.2007.06.042. Epub 2007 Sep 17.
The effects of short-term and long-term diabetes mellitus on urethral function were investigated to determine the contribution of urethral dysfunction to diabetes mellitus voiding dysfunction.
Isovolumetric bladder pressure, urethral perfusion pressure and external urethral sphincter electromyography were measured in urethane anesthetized, female Sprague-Dawley rats (Charles River Laboratories, Wilmington, Massachusetts) 5 or 10 weeks after streptozotocin induced diabetes mellitus. Urethral responses to serial administration of the skeletal muscle blocker alpha-bungarotoxin, the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine and the alpha-adrenergic agonist L-phenylephrine were determined in diabetes mellitus and age matched controls.
Peak bladder pressures and contraction amplitudes were significantly decreased in diabetes mellitus rats. Detrusor-sphincter dyssynergia occurred in approximately 30% of diabetes mellitus rats but never in controls. Alpha-Bungarotoxin caused a greater decrease in baseline urethral perfusion pressure in diabetes mellitus rats than in controls (approximately 40% vs approximately 15%). Bladder contraction associated urethral smooth muscle relaxation amplitudes were significantly less in diabetes mellitus rats than in controls. N(omega)-nitro-L-arginine significantly suppressed urethral relaxation in controls but not in diabetes mellitus rats. L-phenylephrine significantly increased baseline urethral perfusion pressure in diabetes mellitus rats but not in controls. The unassociated conditions of insensitivity to N-nitro-L-arginine and hypersensitivity to L-phenylephrine were more common in 10-week diabetes mellitus rats than in control rats.
Diabetes mellitus induced urethropathy is characterized by external urethral sphincter dysfunction, decreased urethral smooth muscle relaxation and nitric oxide responsiveness, and increased urethral smooth muscle responsiveness to alpha(1)-adrenergic agonists. These changes increase outlet resistance and, thereby, decrease voiding efficiency. This exacerbates voiding dysfunction, creating a vicious cycle of progressive lower urinary tract damage and dysfunction. Early intervention targeting outlet resistance may be indicated.
研究短期和长期糖尿病对尿道功能的影响，以确定尿道功能障碍在糖尿病性排尿功能障碍中的作用。
在链脲佐菌素诱导的糖尿病大鼠（查尔斯河实验室，马萨诸塞州威尔明顿）5周或10周后，对用氨基甲酸乙酯麻醉的雌性斯普拉格-道利大鼠测量等容膀胱压力、尿道灌注压力和尿道外括约肌肌电图。测定糖尿病大鼠和年龄匹配的对照大鼠对连续给予骨骼肌阻滞剂α-银环蛇毒素、一氧化氮合酶抑制剂N（ω）-硝基-L-精氨酸和α-肾上腺素能激动剂L-去氧肾上腺素的尿道反应。
糖尿病大鼠的膀胱峰值压力和收缩幅度显著降低。约30%的糖尿病大鼠出现逼尿肌-括约肌协同失调，而对照组从未出现。α-银环蛇毒素导致糖尿病大鼠的基线尿道灌注压力下降幅度大于对照组（约40%对约15%）。糖尿病大鼠膀胱收缩相关的尿道平滑肌舒张幅度明显小于对照组。N（ω）-硝基-L-精氨酸在对照组中显著抑制尿道舒张，但在糖尿病大鼠中无此作用。L-去氧肾上腺素显著增加糖尿病大鼠的基线尿道灌注压力，但对对照组无此作用。对N-硝基-L-精氨酸不敏感和对L-去氧肾上腺素过敏的非相关情况在10周龄糖尿病大鼠中比在对照大鼠中更常见。
糖尿病性尿道病的特征是尿道外括约肌功能障碍、尿道平滑肌舒张和一氧化氮反应性降低，以及尿道平滑肌对α（1）-肾上腺素能激动剂的反应性增加。这些变化增加了出口阻力，从而降低了排尿效率。这加剧了排尿功能障碍，形成了下尿路进行性损伤和功能障碍的恶性循环。可能需要针对出口阻力进行早期干预。
