Chen Kuo-Chiang, Minor Thomas X, Rahman Nadeem U, Ho Hao-Chung, Nunes Lora, Lue Tom F
Department of Urology, University of California San Francisco, San Francisco, CA, USA.
BJU Int. 2005 May;95(7):1077-80. doi: 10.1111/j.1464-410X.2005.05470.x.
To test the hypothesis that combined intracavernosal injection with vascular endothelial growth factor (VEGF) with adeno-associated virus-mediated brain-derived neurotrophic factor (AAV-BDNF) synergistically facilitates the neural regeneration and erectile function after cavernosal nerve injury.
Forty Sprague-Dawley male rats were randomly divided into five equal groups: eight had a sham operation while 32 had bilateral cavernosal nerve freezing followed by an immediate intracavernosal injection with either phosphate-buffered saline (PBS), VEGF, AAV-BDNF, or AAV-BDNF + VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and samples of the major pelvic ganglia and penile tissue were evaluated histologically.
In this animal model of impotence from nerve injury, the recovery of erectile function was greatest in those receiving AAV-BDNF + VEGF; the mean (sd) maximal intracavernosal pressure in this group was 87.2 (20.78) cmH2O, compared with 37.3 (11.39) for VEGF alone and 49.8 (29.58) for AAV-BDNF alone. No erectile dysfunction was identified in the sham group, with a pressure of 100.7 (22.70) cmH2O, while all treatment groups significantly outperformed the PBS (control) group, at 29.3 (13.52) cmH2O. Furthermore, all animals receiving monotherapy or combined treatment had more NADPH-diaphorase-positive nerve fibres than controls but less than in the sham group.
Bilateral cavernosal nerve freezing causes erectile dysfunction with accompanying neurological changes. Intracavernosal injection with either VEGF or AAV-BDNF alone enhances nerve regeneration, with combined therapy (VEGF and AAV-BDNF) promoting neural and erectile recovery additively.
验证海绵体内联合注射血管内皮生长因子(VEGF)与腺相关病毒介导的脑源性神经营养因子(AAV-BDNF)能协同促进海绵体神经损伤后的神经再生及勃起功能这一假说。
40只雄性Sprague-Dawley大鼠随机分为五组,每组8只。其中8只接受假手术,32只接受双侧海绵体神经冷冻,随后立即海绵体内注射磷酸盐缓冲盐水(PBS)、VEGF、AAV-BDNF或AAV-BDNF + VEGF。3个月时通过海绵体神经电刺激评估勃起功能,并对主要盆腔神经节和阴茎组织样本进行组织学评估。
在这个神经损伤导致阳痿的动物模型中,接受AAV-BDNF + VEGF治疗的大鼠勃起功能恢复最佳;该组海绵体内平均(标准差)最大压力为87.2(20.78)cmH₂O,单独使用VEGF组为37.3(11.39)cmH₂O,单独使用AAV-BDNF组为49.8(29.58)cmH₂O。假手术组未发现勃起功能障碍,压力为100.7(22.70)cmH₂O,而所有治疗组均显著优于PBS(对照)组,后者压力为29.3(13.52)cmH₂O。此外,所有接受单一疗法或联合治疗的动物,其还原型辅酶Ⅱ黄递酶阳性神经纤维均多于对照组,但少于假手术组。
双侧海绵体神经冷冻会导致勃起功能障碍并伴有神经学改变。单独海绵体内注射VEGF或AAV-BDNF均可增强神经再生,联合疗法(VEGF和AAV-BDNF)可相加促进神经和勃起功能的恢复。