Burnett Arthur L, Sezen Sena F, Hoke Ahmet, Caggiano Anthony O, Iaci Jennifer, Lagoda Gwen, Musicki Biljana, Bella Anthony J
Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
J Sex Med. 2015 Apr;12(4):897-905. doi: 10.1111/jsm.12834. Epub 2015 Jan 30.
Erectile dysfunction is a major complication of radical prostatectomy, commonly associated with penile neuropathy. In animal models of peripheral nerve injury, glial growth factor-2 (GGF2), a member of the neuregulin family of growth factors, has neuroprotective and neurorestorative properties, but this potential has not been established after cavernous nerve (CN) injury.
The effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury.
Adult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15 mg/kg) or vehicle subcutaneously 24 hour pre and 24-hour post-BCNI, and once weekly for 5 weeks. Erectile function was assessed in response to electrical stimulation of the CN. CN survival was assessed by fluorogold retrograde axonal tracing in major pelvic ganglia (MPG). Unmyelinated axons in the CNs were quantitated by electron microscopy.
Erectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI.
Erectile function was decreased (P < 0.05) after BCNI, and it was improved (P < 0.05) by all doses of GGF2. The number of fluorogold-labeled cells in the MPG was reduced (P < 0.05) by BCNI and was increased (P < 0.05) by GGF2 (0.5 and 5 mg/kg). The percentage of denervated Schwann cells in the BCNI group was higher (P < 0.05) than that in the sham-treated group and was decreased (P < 0.05) in the GGF2-treated (5 mg/kg) BCNI group. In the BCNI + GGF2 (5 mg/kg) group, the unmyelinated fiber histogram demonstrated a rightward shift, indicating an increased number of unmyelinated axons per Schwann cell compared with the BCNI group.
GGF2 promotes erectile function recovery following CN injury in conjunction with preserving unmyelinated CN fibers. Our findings suggest the clinical opportunity to develop GGF2 as a neuroprotective therapy for radical prostatectomy.
勃起功能障碍是根治性前列腺切除术的主要并发症，通常与阴茎神经病变相关。在周围神经损伤的动物模型中，神经调节蛋白家族生长因子成员之一的胶质细胞生长因子2（GGF2）具有神经保护和神经修复特性，但海绵体神经（CN）损伤后其这种潜力尚未得到证实。
在根治性前列腺切除术相关的CN损伤大鼠模型中，研究GGF2在保持轴突完整性和恢复勃起功能方面的有效性。
成年雄性Sprague-Dawley大鼠接受双侧CN挤压伤（BCNI）或假手术。在BCNI术前24小时和术后24小时，大鼠皮下注射GGF2（0.5、5或15mg/kg）或赋形剂，之后每周一次，持续5周。通过对CN进行电刺激来评估勃起功能。通过在主要盆腔神经节（MPG）中进行荧光金逆行轴突追踪来评估CN的存活情况。通过电子显微镜对CN中的无髓鞘轴突进行定量分析。
BCNI后接受GGF2治疗时，勃起功能恢复情况、CN存活情况以及无髓鞘CN轴突的保留情况。
BCNI后勃起功能下降（P<0.05），所有剂量的GGF2均可使其改善（P<0.05）。BCNI使MPG中荧光金标记细胞数量减少（P<0.05），而GGF2（0.5和5mg/kg）可使其增加（P<0.05）。BCNI组失神经施万细胞的百分比高于假手术组（P<0.05），而GGF2治疗（5mg/kg）的BCNI组该百分比降低（P<0.05）。在BCNI + GGF2（5mg/kg）组中，无髓鞘纤维直方图向右偏移，表明与BCNI组相比，每个施万细胞的无髓鞘轴突数量增加。
GGF2在保护无髓鞘CN纤维的同时，促进CN损伤后的勃起功能恢复。我们的研究结果提示了将GGF2开发为根治性前列腺切除术神经保护疗法的临床可能性。
