| Summary: | 博士 === 中山醫學大學 === 醫學研究所 === 95 === Tacrolimus對於骨盆—尿道反射增益現象的英文摘要
Effects of tacrolimus, a protein phosphatase 2B inhibitor, on the reflex plasticity between the pelvic afferent nerve fibers and the urethra were examined in urethane anesthetized rats. Repetitive stimulation (1 Hz) induced a potentiation (0.9 ± 0.2 and 10.5 ± 1.6 spikes in control and repetitive stimulation groups, respectively, P< 0.01, N= 10) in the activities of the pelvic-urethral reflex. Intrathecal tacrolimus (100 μM, 10μl, bolus) blocked repetitive stimulation- induced potentiation in pelvic-urethral reflex activities (3.2 ± 0.9 spikes in tacrolimus group versus 10.5 ± 1.6 spikes in repetitive stimulation group, P< 0.01, N= 10). Glutamate (intrathecal, 100μM, 10μl, bolus) and N-methyl-D-aspartic acid (intrathecal, 100μM10μl, bolus) both reversed the blocking effects exerted by tacrolimus on repetitive stimulation-induced pelvic-urethral reflex potentiation (15.0 ± 1.4 spikes in glutamate group and 11.4 ± 1.4 spikes in N-methyl-D-aspartic acid group versus 3.2 ± 0.9 spikes in tacrolimus-treated repetitive stimulation group, P< 0.01, N= 7). In addition, the reversal effect elicited by these two agonists of glutamate receptors showed no statistical difference (P= NS, N= 7). All these results demonstrated that tacrolimus could block glutamatergic N-methyl-D-aspartic acid receptor-mediated potentiation in pelvic-urethral reflex activities. This finding may be pathologically relevant in patients who take tacrolimus as immunosuppressant therapy. Whether tacrolimus will induce urine incontinence in such patients or not needs further investigation.
急性單側輸尿管擴張對於骨盆—尿道反射增益現象的影響英文摘要
The effects of acute increase in intra-ureter pressure (IUP) on the pelvic-urethral reflex potentiation were examined in urethane- anesthetized rats by recording the external urethra sphincter electromyogram (EUSE) activities evoked by the pelvic afferent stimulation. When compared with a single action potential elicited by the test stimulation (TS, which is characterized by an intensity that evoked a constant reflex response without facilitation, 1/30 Hz, 1.03 ± 0.12 spikes/stimulation, N= 7), the repetitive stimulation (RS, with the identical stimulation intensity as the test stimulation, 1 Hz) significantly induced spinal reflex potentiation (SRP, 16.90 ± 2.00 spikes/stimulation, P< 0.01, N= 7). Such spinal reflex potentiation was significantly attenuated by intrathecal 2, 3 -dihydroxy-6-nitro- 7-sulfamoyl- benzo (F) quinoxaline [NBQX, a glutamatergic α- amino-3-hydroxy-5-methyl-4-isoxazoleproprionat(AMPA) receptor antagonist] and D-2-amino-5-phosphonovalerate [APV, a glutamatergic N-methyl-D-aspartate (NMDA) antagonist; the spike number per stimulation:11.6 ± 0.71 for NBQX, 1.01 ± 0.30 for APV, and 16.90 ± 2.00 for RS, respectively, P< 0.01, N= 7]. Acute stepwise elevations in the intra-ureter pressure gradually attenuated and eventually abolished the repetitive stimulation- induced spinal reflex potentiation (16.80 ± 1.30, 17.00 ± 1.30, 16.30 ± 1.30, 10.50 ± 1.80, 8.80 ± 1.90, 3.50 ± 1.60, 0.80 ± 0.20, 0.70 ± 0.20 and 0.20 ± 0.10 spikes/stimulation at intra-ureter pressure of 0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5 and 20 cmH2O, respectively, N=7). Intrathecal NMDA (a glutamatergic NMDA receptor agonist) and bicuculline [a gamma amino-butyric acid (GABA) receptor antagonist] both reversed the abolition on repetitive stimulation-induced spinal reflex potentiation caused by the unilateral ureter distension (14.0 ± 4.04 and 8.00 ± 1.53 spikes/stimulation, respectively, N= 7, P< 0.01). All the results suggested unilateral ureter distension might compensatory relax the urethra via a GABAergic inhibition on NMDA-dependent spinal reflex potentiation.
|
|---|
