Laboratory for Experimental Urology, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
J Sex Med. 2014 Jul;11(7):1685-93. doi: 10.1111/jsm.12570. Epub 2014 May 15.
Erectile dysfunction (ED) remains a frequent complication of radical prostatectomy due to injury to the cavernous nerves (CNs). A recent microarray showed the neuropeptide galanin to be one of the most strikingly upregulated genes in the rat major pelvic ganglion (MPG) after bilateral CN crush injury (BCNI).
The aim of this study is to evaluate the temporal regulation of galanin in the MPG after BCNI and its relationship to functional nerve regeneration.
Changes in galanin, galanin receptor (galR), and c-JUN mRNA expression were assessed in Sprague-Dawley rats after sham operation (n = 10) and at 48 hours (n = 10), 7 (n = 10), 14 (n = 5), 21 (n = 5), 30 (n = 5), and 60 (n = 5) days after BCNI using quantitative PCR. Erectile function was assessed by measuring intracavernous pressure (ICP) divided by mean arterial pressure (MAP) during CN electrostimulation. Immunohistochemistry was performed on the MPG in sham-operated animals and 5 days after BCNI.
ICP/MAP upon CN stimulation; galanin, galR1, -2, -3, and c-JUN mRNA expression at various time points after BCNI; and nNOS, galanin, and galR distribution in the MPG of sham-operated rats and after BCNI.
After BCNI, ICP/MAP values quickly deteriorate, while after 60 days, spontaneous restoration of erectile responses to CN stimulation is observed, reflecting CN regeneration. Galanin mRNA in the MPG is up to 186-fold upregulated compared with sham-operated rats at 48 hours and 7 days after BCNI and gradually declines with increasing time from injury, whereas galanin receptor expressions decrease and c-JUN gradually increases. Galanin expression shows a strong inverse correlation with erectile responses to CN stimulation with time from injury. Injured MPGs show a colocalization between galanin- and nNOS-positive neuronal cell population in the MPG.
Galanin is upregulated in the MPG in the early phase after CN injury after which it gradually decreases and is present in nNOS-positive neurons of the ganglion. We hypothesize that galanin upregulation is an important factor in the endogenous neuroregenerative response to CN injury.
由于海绵体神经（CNs）损伤，勃起功能障碍（ED）仍然是根治性前列腺切除术的常见并发症。最近的基因芯片显示，神经肽甘丙肽是大鼠主要盆神经节（MPG）在双侧 CN 挤压损伤（BCNI）后上调最明显的基因之一。
本研究旨在评估 BCNI 后 MPG 中甘丙肽的时间调节及其与功能神经再生的关系。
采用定量 PCR 法检测 Sprague-Dawley 大鼠假手术（n=10）及 BCNI 后 48 小时（n=10）、7 天（n=10）、14 天（n=5）、21 天（n=5）、30 天（n=5）和 60 天（n=5）时甘丙肽、甘丙肽受体（galR）和 c-JUN mRNA 表达的变化。通过 CN 电刺激测量海绵体内压（ICP）与平均动脉压（MAP）的比值来评估勃起功能。在假手术动物和 BCNI 后 5 天对 MPG 进行免疫组织化学染色。
CN 刺激时的 ICP/MAP；BCNI 后不同时间点的甘丙肽、galR1、-2、-3 和 c-JUN mRNA 表达；以及 sham 操作和 BCNI 后 nNOS、甘丙肽和 galR 在 MPG 中的分布。
BCNI 后，ICP/MAP 值迅速恶化，而 60 天后，观察到 CN 刺激的勃起反应自发恢复，反映出 CN 再生。BCNI 后 48 小时和 7 天，MPG 中的甘丙肽 mRNA 上调高达 186 倍，随着损伤时间的延长逐渐下降，而甘丙肽受体表达下降，c-JUN 逐渐增加。甘丙肽的表达与损伤后 CN 刺激的勃起反应呈强烈的负相关。损伤后的 MPG 中甘丙肽与 nNOS 阳性神经元细胞群存在共定位。
CN 损伤后早期 MPG 中甘丙肽上调，随后逐渐下调，并存在于神经节中的 nNOS 阳性神经元中。我们假设甘丙肽的上调是 CN 损伤后内源性神经再生反应的一个重要因素。
