Yoshizawa T, Kadekawa K, Tyagi P, Yoshikawa S, Takahashi R, Takahashi S, Yoshimura N
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Urology, Nihon University School of Medicine, Tokyo, Japan.
Spinal Cord. 2015 Mar;53(3):190-194. doi: 10.1038/sc.2014.233. Epub 2014 Dec 23.
This study investigated the mechanisms inducing autonomic dysreflexia due to enhanced bladder-to-vascular reflexes in rats with spinal cord injury (SCI).
SCI was produced by the transection of the Th4-5 spinal cord in female Sprague-Dawley rats. At 4 weeks after SCI, changes in blood pressure during graded increases in intravesical pressure (20-60 cm HO) were measured in spinal-intact (SI) and SCI rats under urethane anesthesia. In five animals, effects of C-fiber desensitization induced by intravesical application of resiniferatoxin (RTX), a TRPV1 agonist, on the bladder-to-vascular reflex were also examined. Nerve growth factor (NGF) levels of mucosa and detrusor muscle layers of the bladder were measured by enzyme-linked immunosorbent assay. The expression levels of TRPV1 and TRPA1 channels were also examined in laser captured bladder afferent neurons obtained from L6 DRG, which were labeled by DiI injected into the bladder wall.
In SI and SCI rats, systemic arterial blood pressure was increased in a pressure-dependent manner during increases in the intravesical pressure, with significantly higher blood pressure elevation at the intravesical pressure of 20 cm HO in SCI rats vs SI rats. The arterial blood pressure responses to bladder distention were significantly reduced by RTX-induced desensitization of C-fiber bladder afferent pathways. SCI rats had higher NGF protein levels in the bladder and higher TRPV1 and TRPA1 mRNA levels in bladder afferent neurons compared with SI rats.
The bladder-to-vascular reflex induced by TRPV1-expressing C-fiber afferents during bladder distention is enhanced after SCI in association with increased expression of NGF in the bladder and TRP channels in bladder afferent neurons.
本研究探讨脊髓损伤（SCI）大鼠膀胱-血管反射增强导致自主神经反射异常的机制。
采用雌性Sprague-Dawley大鼠，通过横断胸4-5脊髓制造SCI模型。SCI术后4周，在乌拉坦麻醉下，测量脊髓完整（SI）和SCI大鼠膀胱内压分级升高（20-60 cm H₂O）时的血压变化。在5只动物中，还研究了膀胱内应用树脂毒素（RTX，一种TRPV1激动剂）诱导的C纤维脱敏对膀胱-血管反射的影响。采用酶联免疫吸附测定法测量膀胱黏膜和逼尿肌层的神经生长因子（NGF）水平。还检测了从L6背根神经节获取的经DiI注入膀胱壁标记的激光捕获膀胱传入神经元中TRPV1和TRPA1通道的表达水平。
在SI和SCI大鼠中，膀胱内压升高时，全身动脉血压呈压力依赖性升高，SCI大鼠在膀胱内压为20 cm H₂O时的血压升高明显高于SI大鼠。RTX诱导的C纤维膀胱传入通路脱敏显著降低了动脉血压对膀胱扩张的反应。与SI大鼠相比，SCI大鼠膀胱中的NGF蛋白水平更高，膀胱传入神经元中的TRPV1和TRPA1 mRNA水平更高。
SCI后，膀胱扩张时由表达TRPV1的C纤维传入神经诱导的膀胱-血管反射增强，这与膀胱中NGF表达增加以及膀胱传入神经元中TRP通道表达增加有关。
