Effects of liposome-based local suppression of nerve growth factor in the bladder on autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury
Effects of liposome-based local suppression of nerve growth factor in the bladder on autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury
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DOI：
10.1016/j.expneurol.2017.01.014
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发表时间：
2017-05-01
影响因子：
5.3
通讯作者：
Yoshimura, Naoki
中科院分区：
文献类型：
--
作者：
Kadekawa, Katsumi;Yoshizawa, Tsuyoshi;Yoshimura, Naoki
目的：研究（1）脊髓损伤（SCI）是否时间依赖性地增加自主神经反射异常（AD）的严重程度和膀胱神经生长因子（NGF）蛋白的表达水平，以及（2）是否在膀胱局部抑制NGF改善SCI诱导的AD大鼠。材料和方法：SCI是由横断的T2/3脊髓雌性SD大鼠。在脊髓损伤后4或8周，在尿烷麻醉下，在脊髓完整和脊髓损伤大鼠中，在膀胱内压力从膀胱扩张前的水平逐渐增加到20、40和60 cm H2O期间，评估平均动脉血压（Delta MAP）和心率（Delta MHR）的差异以及膀胱壁中的NGF蛋白水平。SCI后7周，将脂质体-NGF反义缀合物膀胱内施用至动物。结果：脊髓损伤大鼠膀胱内压20、40、60 cm H2O时，膀胱扩张时Δ MAP、Δ MHR呈递增趋势，膀胱扩张时Δ MAP、Δ MHR呈递增趋势，膀胱扩张时Δ MAP、Δ MHR呈递增趋势。脊髓损伤后，这些AD样心血管反应和膀胱粘膜和肌肉层中的NGF蛋白表达以时间依赖的方式增加。脂质体-NGF反义治疗显著降低了SCI大鼠膀胱粘膜层中NGF蛋白的过表达，并降低了膀胱扩张引起的Δ MAP和Δ MHR。这些结果表明SCI后恢复期的持续时间影响膀胱扩张诱导的AD的严重程度以及膀胱NGF蛋白水平，并且膀胱中NGF表达的局部抑制减少SCI诱导的AD。因此，膀胱内应用脂质体-NGF反义偶联物可能是一种新的有效治疗脊髓损伤后膀胱扩张诱导的AD的方法。(C)2017爱思唯尔公司All rights reserved.
Purpose: To examine (1) whether spinal cord injury (SCI) time-dependently increases the severity of autonomic dysreflexia (AD) and expression levels of bladder nerve growth factor (NGF) protein, and (2) whether local suppression of NGF in the bladder improves SCI-induced AD in rats.Materials and methods: SCI was produced by the transection of the T2/3 spinal cord in female Sprague-Dawley rats. At 4 or 8 weeks after SCI, differences in the mean arterial blood pressure (Delta MAP) and heart rate (Delta MHR) during graded increases in intravesical pressure to 20, 40 and 60 cm H2O from those before bladder distention and NGF protein levels in the bladder wall were evaluated in spinal intact and SCI rats under urethane anesthesia. Seven weeks after SCI liposome-NGF antisense conjugates were administered intravesically to the animals. At 1 week after intravesical treatment (8 weeks after SCI), Delta MAP and Delta MHR during bladder distention and bladder NGF protein expression were evaluated.Results: The Delta MAP and Delta MHR were increased in a graded manner in response to bladder distention at intravesical pressures of 20, 40 and 60 cm H2O in SCI rats. These AD-like cardiovascular responses and NGF protein expression in the bladder mucosal and muscle layers were increased after SCI in a time-dependent manner. The liposome-NGF antisense treatment significantly reduced the NGF protein overexpression in the mucosal layer of SCI rat bladder and reduced Delta MAP and Delta MHR elicited by bladder distention.Conclusions: These results indicate that the duration of the post-SCI recovery period affects the severity of AD induced by bladder distention as well as the level of bladder NGF protein, and that local suppression of NGF expression in the bladder reduces SCI-induced AD. Thus, Intravesical application of liposome-NGF antisense conjugates can be a new effective therapy for bladder distention-induced AD after SCI. (C) 2017 Elsevier Inc. All rights reserved.