神經調控對逼尿肌-括約肌協同失調大白鼠的膀胱功能影響

Abstract

膀胱功能障礙常好發於脊髓損傷或糖尿病。少有文獻探討會陰神經調控對於膀胱功能的可行性。此研究的兩大目的: 第一，判定六周脊髓損傷大白鼠在會陰神經電刺激下，提升排尿功能的影響；第二，判定三周或六周糖尿病大白鼠在慢性會陰神經微電流刺激下，對於排尿功能之影響，並探討其相關神經調控機制。 對於脊髓損傷大白鼠，利用兩種尿液動力量測來評估電刺激對於膀胱及尿道功能:在連續膀胱頂灌注下，同步量測等張力膀胱內壓及外尿道括約肌肌電圖；及在膀胱同體積灌注下，同步量測等體積膀胱內壓及外尿道灌注內壓。對於糖尿病大白鼠，為評估微電流刺激對於膀胱與尿道功能，在連續膀胱頂灌注下，同步量測等張力膀胱內壓、外尿道括約肌肌電圖及尿液流速。 對於脊髓損傷大白鼠，結果顯示其不正常的膀胱測壓量測，包括容量閾值、膀胱收縮壓及餘尿容量的增加，表示大白鼠在六周脊髓損傷後的排尿功能障礙。在脊髓損傷後，排尿效率下降至13%，而在會陰神經電刺激後，可提升至22% - 34%。此外，會陰神經電刺激顯著增加外尿道括約肌的波動時期，並增加未排尿期尿道內壓與排尿期高頻震盪尿道內壓的壓力差，及改變膀胱與外尿道活動的時間差。 另一方面，對於三周或六周糖尿病鼠的排尿功能障礙，其結果顯示出容量閾值、膀胱收縮壓及膀胱時期的增加。未接受微電刺激的六周糖尿病鼠，其排尿效率下降至18%，相對地，接受微電刺激的六周糖尿病鼠，其排尿效率仍維持在50%。此外會陰神經為電刺激顯著改變糖尿病鼠的外尿道括約肌波動時期、尿液流速平均值及流動時期。 總合上述發現，會陰神經調控可增長排尿時間，減少外尿道阻力，並恢復逼尿肌-括約肌協同失調的情形，進而可提升脊髓損傷鼠的排尿效率。對於糖尿病鼠，會陰神經微電刺激可增加尿液平均流速並減緩會陰神經病變，進而提升其排尿效率。 本研究證實會陰神經調控在慢性脊髓損傷或糖尿病鼠，對於膀胱功能障礙改善的可行性。這些結果可作為研發臨床恢復膀胱功能的神經輔具之基礎。

Bladder dysfunction often occurs in spinal cord injury (SCI) or diabetes mellitus. Few studies have explored the feasibility of pudendal neuromodulation in regulating bladder functions. Two aims of the present study: the first was electrical activation of the pudendal sensory branch in improving voiding functions in rats 6 weeks after a SCI and the second was chronic microstimulation of the pudendal sensory branch in improving the voiding functions in diabetic rats for 3 or 6 weeks. To assess the effects of electrical stimulation (ES) on bladder and urethral functions, there were two urodynamic measurements for SCI rats: simultaneous recordings of the intravesical pressure (IVP) during continuous isotonic transvesical infusion (isotonic IVP) and external urethral sphincter-electromyography (EUS-EMG), and simultaneous recordings of transvesical pressure under isovolumetric conditions (isovolumetric IVP) and urethral perfusion pressure (UPP). And for electrical microstimulation diabetic rats, the effects of on bladder and urethral functions were assessed by simultaneous recordings of the IVP during continuous isotonic IVP, EUS-EMG, and urine flow rate (UFR). For SCI rats, our results revealed abnormal cystometric measurements, including increases in the volume threshold (VT), contraction amplitude (CA), and residual volume as well as decreased voided volume, which indicated voiding dysfunction in rats 6 weeks after an SCI. The voiding efficiency (VE) decreased to 13% after the SCI, which increased to 22%~34% after applying pudendal afferent stimulation. In addition, pudendal stimulation significantly increased the EUS burst period (EUS-BP) and the difference between the UPP and the high-frequency oscillation (HFO) baselines, and changed the time offset between bladder and EUS activities. On the other hand, our results revealed abnormal cystometric measurements, including increases in the VT, CA, and contraction duration, which indicated voiding dysfunction in diabetic rats of 3 or 6 weeks. The VE decreased to 18% at diabetic rats with sham ES of 6 weeks, which increased to ~50% after applying chronic pudendal microstimulation of 6 weeks. In addition, chronic pudendal microstimulation significantly changed the EUS-BP, mean of UFR and flow duration. All of these findings suggest that pudendal afferent stimulation improved the VE by prolonging the micturition interval, decreasing the urethral resistance, and recovering the detrusor-sphincter dyssynergia during the voiding phase in SCI rats and chronic pudendal microstimulation improved the VE by increasing mean of UFR, and reducing diabetic neuropathy on pudendal nerve in diabetic rats. This study demonstrates the feasibility of pudendal neuromodulation in rats with chronic SCI or chronic diabetes. These results could be as the base for developing an advanced neural prosthesis to restore bladder function in clinical settings.