The effect of vascular endothelial growth factor and brain-derived neurotrophic factor on cavernosal nerve regeneration in a nerve-crush rat model

The effect of vascular endothelial growth factor and brain-derived neurotrophic factor on cavernosal nerve regeneration in a nerve-crush rat model
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DOI:
10.1046/j.1464-410x.2003.04373.x
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发表时间:
2003-09-01
期刊:
影响因子:
4.5
通讯作者:
Lue, TF
Lue, TF
中科院分区:
医学2区
文献类型:
--
作者:
Hsieh, PS;Bochinski, DJ;Lue, TF

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为验证海绵体内注射脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)能促进海绵体神经损伤后的神经再生和勃起功能的恢复。四个人做了假手术,七个人双侧神经挤压没有进一步的干预,14例双侧神经夹伤,立即(7例)或延迟1个月(7例)海绵体内注射BDNF+VEGF。3个月时通过电刺激海绵体神经评估勃起功能,并通过NADPH黄递酶染色和酪氨酸羟化酶(TH)染色阴茎组织和主要盆神经节(MPG)评估神经再生。神经压榨后,3个月时的功能评估显示海绵体神经刺激的平均(SD)海绵体内压(ICP)较低,为33.9(15.3)cmH(2)O,假手术组为107.8(18.1)cmH(2)O。立即注射BDNF+VEGF后,ICP显著高于对照组,为67.8(38.5)cmH(2)O。即使延迟注射BDNF+VEGF也能改善ICP,至78.0(21.8)cmH2 O。NADPH和TH染色标本的组织学分析表明,海绵体和背神经的终末分支的形态学的显着变化,和MPG中的神经元的染色质量。经脑源性神经营养因子+血管内皮生长因子处理后,阳性染色的神经纤维数量趋于恢复正常。海绵体内注射脑源性神经营养因子+血管内皮生长因子似乎既能防止MPG、背神经和海绵体内组织中含有神经元一氧化氮合酶的神经元变性,又能促进其再生。因此,它可能具有促进根治性盆腔手术后勃起功能恢复的治疗潜力。
To test the hypothesis that an intracavernosal injection with brain-derived neurotrophin factor (BDNF) and vascular endothelial growth factor (VEGF) can facilitate nerve regeneration and recovery of erectile function after cavernosal nerve injury.The study included 25 Sprague-Dawley rats; four had a sham operation, seven bilateral nerve crushing with no further intervention, and 14 bilateral nerve crushing with either an immediate (seven) or delayed for 1 month (seven) intracavernosal injection with BDNF+VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and neural regeneration by NADPH-diaphorase staining and tyrosine hydroxylase (TH) staining of penile tissue and major pelvic ganglia (MPG).After nerve crushing, the functional evaluation at 3 months showed a lower mean (SD) intracavernosal pressure (ICP) with cavernosal nerve stimulation, at 33.9 (15.3) cmH(2)O, than in the sham group, at 107.8 (18.1) cmH(2)O. With an immediate injection with BDNF+VEGF the ICP was significantly higher than in the controls, at 67.8 (38.5) cmH(2)O. Even delayed injection with BDNF+VEGF improved the ICP, to 78.0 (21.8) cmH(2)O. Histological analysis of specimens stained for NADPH and TH showed a significant change in the morphology of terminal branches of the cavernosal and dorsal nerves, and the staining quality of the neurones in the MPG. The number of positively stained nerve fibres tended to revert to normal after treatment with BDNF+VEGF.An intracavernosal injection with BDNF+VEGF appears to both prevent degeneration and facilitate regeneration of neurones containing neuronal nitric oxide synthase in the MPG, dorsal nerve and intracavernosal tissue. Therefore it might have therapeutic potential for enhancing the recovery of erectile function after radical pelvic surgery.