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血管内皮生长因子和脑源性神经营养因子对神经挤压大鼠模型海绵体神经再生的影响。

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

作者信息

Hsieh P-S, Bochinski D J, Lin G T, Nunes L, Lin C S, Lue T F

机构信息

Department of Urology, University of California, San Francisco, CA 94143, USA.

出版信息

BJU Int. 2003 Sep;92(4):470-5. doi: 10.1046/j.1464-410x.2003.04373.x.

Abstract

OBJECTIVE

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.

MATERIALS AND METHODS

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).

RESULTS

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) cmH2O, than in the sham group, at 107.8 (18.1) cmH2O. With an immediate injection with BDNF+VEGF the ICP was significantly higher than in the controls, at 67.8 (38.5) cmH2O. Even delayed injection with BDNF+VEGF improved the ICP, to 78.0 (21.8) cmH2O. 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.

CONCLUSION

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.

摘要

目的

验证如下假设,即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)可促进海绵体神经损伤后神经再生及勃起功能恢复。

材料与方法

本研究纳入25只Sprague-Dawley大鼠;4只接受假手术,7只双侧神经挤压且无进一步干预,14只双侧神经挤压后立即(7只)或延迟1个月(7只)进行海绵体内注射BDNF+VEGF。3个月时通过海绵体神经电刺激评估勃起功能,通过阴茎组织和主盆腔神经节(MPG)的NADPH-黄递酶染色和酪氨酸羟化酶(TH)染色评估神经再生。

结果

神经挤压后,3个月时的功能评估显示,海绵体神经刺激时平均(标准差)海绵体内压(ICP)为33.9(15.3)cmH2O,低于假手术组的107.8(18.1)cmH2O。立即注射BDNF+VEGF后,ICP显著高于对照组,为67.8(38.5)cmH2O。即使延迟注射BDNF+VEGF也可使ICP改善至78.0(21.8)cmH2O。对NADPH和TH染色的标本进行组织学分析显示,海绵体神经和背神经终末分支形态以及MPG中神经元的染色质量有显著变化。用BDNF+VEGF治疗后,阳性染色神经纤维数量趋于恢复正常。

结论

海绵体内注射BDNF+VEGF似乎既能防止MPG、背神经和海绵体内组织中含神经元型一氧化氮合酶的神经元变性,又能促进其再生。因此,其可能对增强根治性盆腔手术后勃起功能的恢复具有治疗潜力。

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