海绵体内生长分化因子-5治疗对海绵体神经损伤大鼠模型的影响。

The effect of intracavernosal growth differentiation factor-5 therapy in a rat model of cavernosal nerve injury.

作者信息

Fandel Thomas M, Bella Anthony J, Tantiwongse Kavirach, Garcia Maurice, Nunes Lora, Thüroff Joachim W, Tanagho Emil A, Pohl Jens, Lue Tom F

机构信息

Johannes Gutenberg-University School of Medicine, Mainz, Germany.

出版信息

BJU Int. 2006 Sep;98(3):632-6. doi: 10.1111/j.1464-410X.2006.06375.x. Epub 2006 Jun 26.

DOI:10.1111/j.1464-410X.2006.06375.x

PMID:16796696

Abstract

OBJECTIVE

To determine whether the intracavernosal application of growth differentiation factor-5 (GDF-5) influences nerve regeneration and erectile function after cavernosal nerve injury in a rat model.

MATERIALS AND METHODS

Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: eight had a sham operation (uninjured controls), while 24 had bilateral cavernosal nerve crush. The crush-injury groups were treated at the time of injury with an impregnated collagen sponge implanted into the right corpus cavernosum. The sponge contained no GDF-5 (injured controls), 2 microg (low concentration), or 20 microg GDF-5 (high concentration). Erectile function was assessed by cavernosal nerve electrostimulation at 8 weeks. Midshaft penile tissue samples were histochemically evaluated for neuronal nitric oxide synthase (nNOS)-containing fibres in the dorsal penile nerve.

RESULTS

There was no erectile dysfunction in the uninjured control group, as shown by a mean (sem) maximal increase in intracavernosal pressure (ICP) of 149.5 (17.0) cmH(2)O on stimulation. By comparison, the ICP decreased in the injured control group, by 21.3 (6.7) cmH(2)O. After cavernosal nerve injury, the recovery of erectile function was greatest in the low-concentration GDF-5 group; the maximum ICP increase was 40.8 (13.3) cmH(2)O, vs 24.3 (5.9) cmH(2)O for 20 microg GDF-5. Histologically, the low-concentration group had significantly more nNOS-containing nerve fibres, at 163 (24.7), than the high-concentration group, at 76 (17.3), or injured controls, at 67 (23.8). By contrast, the uninjured controls had a mean of 538 (40.6) nerve fibres in the dorsal nerve.

CONCLUSION

Bilateral cavernosal nerve crush resulted in erectile dysfunction with accompanying neurological changes in the rat. The intracavernosal application of GDF-5 enhanced the recovery of erectile function and n-NOS nerve preservation, with a 2-microg dose giving the most promising results.

摘要

目的

在大鼠模型中确定海绵体内应用生长分化因子-5（GDF-5）是否会影响海绵体神经损伤后的神经再生和勃起功能。

材料与方法

32只雄性Sprague-Dawley大鼠被随机分为四组，每组8只：8只接受假手术（未损伤对照组），24只接受双侧海绵体神经挤压。挤压损伤组在损伤时用植入右侧海绵体的含药胶原海绵进行治疗。海绵中不含GDF-5（损伤对照组）、2微克（低浓度）或20微克GDF-5（高浓度）。8周时通过海绵体神经电刺激评估勃起功能。对阴茎中轴组织样本进行组织化学评估，以检测阴茎背神经中含神经元型一氧化氮合酶（nNOS）的纤维。

结果

未损伤对照组无勃起功能障碍，刺激时海绵体内压（ICP）平均（标准误）最大增加149.5（17.0）cmH₂O。相比之下，损伤对照组的ICP下降了21.3（6.7）cmH₂O。海绵体神经损伤后，低浓度GDF-5组勃起功能恢复最佳；最大ICP增加为40.8（13.3）cmH₂O，而20微克GDF-5组为24.3（5.9）cmH₂O。组织学上，低浓度组含nNOS的神经纤维明显多于高浓度组，分别为163（24.7）条和76（17.3）条，也多于损伤对照组的67（23.8）条。相比之下，未损伤对照组阴茎背神经平均有538（40.6）条神经纤维。