Hannan Johanna L, Albersen Maarten, Stopak Bernard L, Liu Xiaopu, Burnett Arthur L, Hoke Ahmet, Bivalacqua Trinity J
The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, Maryland.
J Neurosci Res. 2015 Jun;93(6):954-63. doi: 10.1002/jnr.23553. Epub 2015 Jan 19.
Despite nerve-sparing radical prostatectomy, nerve damage and erectile dysfunction (ED) prevail, and preventing neurodegeneration is of great importance. Neurotrophic factors and neurite outgrowth were characterized in major pelvic ganglia (MPG) following bilateral cavernous nerve injury (BCNI). Young male Sprague-Dawley rats underwent sham or BCNI surgery, and the intracavernosal pressure to mean arterial pressure ratio was measured 2, 7, 14, 21, 30, and 60 days following injury (n = 8/group). MPG gene expression (qPCR) and Western blot were performed for glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurturin, neurotrophin (NT)-3, NT4, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and activating transcription factor 3 (ATF3). Additional rats were injured, and MPGs were removed 24 hr, 48 hr, 3 days, and 7 days following BCNI (n = 3/group). MPGs were cultured in Matrigel, and neurite outgrowth was measured. Erections were impaired early and improved by 60 days in BCNI rats. GDNF, NGF, BDNF, and ATF3 gene expression was significantly increased and NT3 was decreased in MPGs following BCNI (48 hr to 21 days, P < 0.05). GDNF and NGF protein levels were elevated in 48-hr BCNI rats. MPG neurite outgrowth from 24-hr and 48-hr BCNI was higher than sham (658 ± 19 μm, 607 ± 24 μm, 393 ± 23 μm, respectively, P < 0.05). Further studies examining the roles of neurotrophic factors in modulating signaling pathways may provide therapeutic avenues for neurogenically mediated ED.
尽管进行了保留神经的根治性前列腺切除术，但神经损伤和勃起功能障碍（ED）仍然普遍存在，因此预防神经变性非常重要。在双侧海绵体神经损伤（BCNI）后，对主要盆腔神经节（MPG）中的神经营养因子和神经突生长进行了表征。对年轻雄性Sprague-Dawley大鼠进行假手术或BCNI手术，并在损伤后2、7、14、21、30和60天测量海绵体内压与平均动脉压的比值（每组n = 8）。对MPG进行基因表达（qPCR）和蛋白质印迹分析，检测胶质细胞系源性神经营养因子（GDNF）、神经生长因子（NGF）、神经营养素、神经营养因子（NT）-3、NT4、脑源性神经营养因子（BDNF）、血管内皮生长因子和激活转录因子3（ATF3）。另外的大鼠受伤后，在BCNI后24小时、48小时、3天和7天切除MPG（每组n = 3）。将MPG培养在基质胶中，并测量神经突生长。BCNI大鼠的勃起功能早期受损，60天时有所改善。BCNI后MPG中GDNF、NGF、BDNF和ATF3基因表达显著增加，NT3减少（48小时至21天，P < 0.05）。48小时BCNI大鼠中GDNF和NGF蛋白水平升高。24小时和48小时BCNI组的MPG神经突生长高于假手术组（分别为658±19μm、607±24μm、393±23μm，P < 0.05）。进一步研究神经营养因子在调节信号通路中的作用可能为神经源性介导的ED提供治疗途径。
