Fandel Thomas M, Bella Anthony J, Lin Guiting, Tantiwongse Kavirach, Lin Ching-Shwun, Pohl Jens, Lue Tom F
University of California, San Francisco-Urology, San Francisco, CA 94143-0738, USA.
J Sex Med. 2008 Aug;5(8):1866-75. doi: 10.1111/j.1743-6109.2008.00881.x. Epub 2008 Jun 28.
Neurogenic erectile dysfunction remains a serious complication in the postprostatectomy population. Effective protective and regenerative neuromodulatory strategies are needed.
To determine the effect of growth differentiation factor-5 (GDF-5) on erectile function and its mechanism in a rat model of cavernous nerve (CN) injury.
Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissues were examined by real-time polymerase chain reaction (PCR) and immunohistochemical analyses.
Forty-eight male Sprague-Dawley rats were randomly divided into six equal groups: one group underwent sham operation (uninjured controls), while five groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of a slow-release suspension of liquid microparticles containing no GDF-5 (vehicle), 0.4 microg (low concentration), 2 microg (intermediate concentration), or 10 microg GDF-5 (high concentration). One untreated group served as injured controls.
GDF-5 enhanced erectile recovery and significantly increased intracavernous pressure in the low and intermediate-concentration groups vs. injured controls. Low-concentration GDF-5 demonstrated the best functional preservation, as the intracavernous pressure increase in this group did not differ significantly from uninjured controls. A dose-response relationship was confirmed for the effects of GDF-5 in penile tissue. Low-concentration GDF-5 showed better preservation of the penile dorsal nerves and antiapoptotic effects in the corpus cavernosum (P < 0.05 vs. injured controls). Although high concentration GDF-5 did not confer meaningful erectile recovery, this dose was more effective at decreasing transforming growth factor-beta than low-concentration GDF-5.
Intracavernous injection of low (0.4 microg) or intermediate-concentration GDF-5 (2 microg) was effective in preserving erectile function in a rat model of neurogenic erectile dysfunction. The underlying mechanism appears to involve neuron preservation and antiapoptosis.
神经源性勃起功能障碍仍是前列腺切除术后患者的严重并发症。需要有效的保护性和再生性神经调节策略。
确定生长分化因子-5（GDF-5）对海绵体神经（CN）损伤大鼠模型勃起功能的影响及其机制。
4周时通过CN电刺激评估勃起功能。通过实时聚合酶链反应（PCR）和免疫组织化学分析检查阴茎组织。
48只雄性Sprague-Dawley大鼠随机分为6组，每组数量相等：一组接受假手术（未损伤对照组），而五组接受双侧CN挤压。挤压损伤组在损伤时通过海绵体内注射不含GDF-5的液体微粒缓释悬浮液（赋形剂）、0.4微克（低浓度）、2微克（中浓度）或10微克GDF-5（高浓度）进行治疗。一组未治疗组作为损伤对照组。
与损伤对照组相比，低浓度和中浓度组的GDF-5增强了勃起恢复并显著增加了海绵体内压。低浓度GDF-5显示出最佳的功能保留，因为该组海绵体内压的增加与未损伤对照组无显著差异。证实了GDF-5对阴茎组织作用的剂量反应关系。低浓度GDF-5在阴茎背神经的保留和海绵体抗凋亡作用方面表现更好（与损伤对照组相比，P<0.05）。虽然高浓度GDF-5未带来有意义的勃起恢复，但该剂量在降低转化生长因子-β方面比低浓度GDF-5更有效。
海绵体内注射低浓度（0.4微克）或中浓度（2微克）GDF-5可有效保留神经源性勃起功能障碍大鼠模型的勃起功能。其潜在机制似乎涉及神经元保留和抗凋亡作用。
