Kwon Dongdeuk, Minnery Brandon, Kim Yongtae, Kim Jang Hwan, de Miguel Fernando, Yoshimura Naoki, Chancellor Michael B
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Urology. 2005 Jun;65(6):1249-53. doi: 10.1016/j.urology.2005.01.037.
To create a model of peripheral neuropathy and explore the potential of using muscle-derived cells (MDCs) to facilitate the regeneration of autonomic nerves and improve bladder function. Damage to the peripheral nerves that innervate the bladder from radical pelvic surgery is refractory to the currently available treatments.
Rat MDCs were isolated from the gastrocnemius muscle using the preplate technique. The unilateral pelvic nerve was cut in female Sprague-Dawley rats. Three experimental groups were included: control (n = 5); unilateral pelvic nerve transected with sham injection (n = 5); and unilateral pelvic nerve transected with injection of MDC (3 x 10(5) cells/site; n = 5). Two weeks after injection, the intravesical pressures were measured during electrical stimulation of the proximal transected preganglionic nerve. The contralateral major pelvic ganglion was excised to ensure that any observed bladder activity was due exclusively to inputs on the unilateral side. The rats were killed, the experimental side major pelvic ganglion was removed, and enkephalin immunoreactivity was counted.
After unilateral pelvic nerve transection, no change occurred in bladder weight or capacity or postvoid residual urine volume. The maximal intravesical pressures for the control, sham, and MDC groups, after the contralateral pelvis had been cut, was 31.7 +/- 10.3, 9.6 +/- 4.5, and 15.2 +/- 7.7 cm H2O, respectively (P <0.05). After transecting the preganglionic pelvic nerve, the intensity of pericellular enkephalin immunoreactivity varicosities was significantly decreased in the sham group but unchanged in the MDC group compared with the control group.
MDCs can promote peripheral autonomic nerve regeneration. The morphologic changes correlated with the functional neurologic recovery effect of MDCs. The underlying neurologic recovery mechanisms of MDCs need to be exploited.
建立周围神经病变模型,探讨利用肌肉衍生细胞(MDCs)促进自主神经再生及改善膀胱功能的潜力。根治性盆腔手术导致支配膀胱的周围神经损伤,目前的治疗方法对此疗效不佳。
采用预板层技术从大鼠腓肠肌中分离出MDCs。在雌性Sprague-Dawley大鼠中切断单侧盆腔神经。分为三个实验组:对照组(n = 5);单侧盆腔神经切断并假注射组(n = 5);单侧盆腔神经切断并注射MDC组(3×10⁵个细胞/部位;n = 5)。注射两周后,在电刺激近端切断的节前神经时测量膀胱内压。切除对侧主盆腔神经节,以确保观察到的膀胱活动仅源于单侧输入。处死大鼠,取出实验侧主盆腔神经节,计数脑啡肽免疫反应性。
单侧盆腔神经切断后,膀胱重量、容量及残余尿量均无变化。在切断对侧骨盆后,对照组、假注射组和MDC组的最大膀胱内压分别为31.7±10.3、9.6±4.5和15.2±7.7 cm H₂O(P<0.05)。切断节前盆腔神经后,与对照组相比,假注射组细胞周围脑啡肽免疫反应性曲张强度显著降低,而MDC组无变化。
MDCs可促进周围自主神经再生。形态学变化与MDCs的功能性神经恢复效果相关。MDCs潜在的神经恢复机制有待进一步研究。