神经延期移植修复损伤的阴茎海绵体神经恢复大鼠勃起功能

阴茎勃起功能障碍（ED）是盆腔根治性手术后常见并发症之一。随着对勃起通路的认识和显微外科技术的发展，重建勃起通路恢复患者自发勃起功能正成为可能。临床中应用自体神经一期移植修复损伤的海绵体神经（CN），可以恢复部分男性患者的勃起功能。而许多情况下，一期手术修复损伤的海绵体神经很困难，需延期修复。本研究旨在应用自体腓肠神经延期移植修复外科损伤的海绵体神经，重建大鼠勃起通路的可行性。     

海绵体脚结扎术后阴茎持续勃起

双侧阴茎海绵体脚结扎辅以阴茎背深静脉结扎,是治疗静脉性勃起功能障碍(ED),较有效的方法之一。目前研究静脉性ED的手术方法和疗效较多,对术后并发症及其处理的研究则较少。本文对本科1995年1月至2001年6月收治的31例静脉性ED患者,在行海绵体脚结扎术后发生阴茎持续勃起状况及处理方法进行分析、讨论。现报告如下。     

勃起功能障碍患者及不同年龄与正常人阴茎海绵体平滑肌组织学观察

目的：了解正常及勃起功能障碍（ED）患者阴茎海绵体的差异和改变对阴茎勃起的影响。方法：取10例不同年龄正常及ED病人阴茎海绵体组织，镜下观察阴茎海绵体结构变化。结果：3例ED病人阴茎海绵体平滑肌细胞及弹力纤维减少。老年性阴茎海绵体平滑肌及弹力纤维明显减少。青壮年阴茎海绵体平滑肌细胞及弹力纤维极为丰富。结论：阴茎海绵体结构改变对阴茎勃起功能有较大的影响。     

阴茎海绵体药物注射治疗勃起功能障碍19年1例报告

阴茎勃起功能障碍(ED)是指阴茎不能勃起和(或)不能维持勃起以达到满意的性生活,是男性最常见的性功能障碍之一.ED的治疗方法多种多样,有第一线的口服药物和负压式辅助装置等;第二线的阴茎海绵体内药物注射(ICI)以及经尿道内给药;第三线的假体植入手术治疗等([1]).     

阴茎海绵体神经重建术研究进展

阴茎海绵体神经损伤是导致勃起功能障碍(ED)的常见原因,海绵体神经重建修复有望恢复患者性功能。海绵体神经重建的方法有直接吻合、自体神经移植以及可降解生物材料的替代,目前应用于临床的只有自体腓肠神经移植。神经重建过程中,神经生长因子也起重要作用。本文就近年阴茎海绵体神经的重建方法作一综述。     

阴茎异常勃起15例临床分析

阴茎异常勃起是男科急症，长时间勃起可导致海绵体组织损伤，继发勃起功能障碍。1990年-2004年，我科共收治阴茎异常勃起患者15例，现就有关诊治情况报道如下。     

马尾神经损伤后阴茎海绵体注射诱发异常勃起1例

患者 ,37岁。 1年前在外院行腰4～5椎间盘摘除术 ,术后出现阴茎勃起障碍、排尿困难不适等症状 ,曾再次行“马尾神经松解植骨术” ,但术后上述症状缓解不明显。入院前 1d行双下肢体感诱发电位检查显示异常 ;尿流率检查提示梗阻曲线。因F8导尿管不能插入尿道 ,故无法进行尿动力学检查(其间有少许尿道出血 ,患者拒绝进一步检查 )。2 0 0 2年 1 0月 9日来我院进行性功能测定。入院后体检 :会阴部感觉减退 ,阴茎痛觉消失 ,触觉存在 ,球海绵体反射消失 ,左下肢肌力Ⅳ级 ,感觉迟钝 ,右下肢肌力Ⅴ级 ,感觉正常。行Rigiscan加AVSS检查阴茎无勃起。…     

海绵体神经损伤性勃起功能障碍治疗研究进展

随着前列腺手术的广泛开展和骨盆骨折尿道损伤患者的不断增多,海绵体神经损伤性阴茎勃起功能障碍越来越受到关注。海绵体神经损伤后,阴茎平滑肌和内皮细胞凋亡,NOS阳性神经密度降低,进而出现海绵体平滑肌纤维化。损伤后的神经再生策略一直是ED研究的热点之一。本综述将围绕促进海绵体神经再生的治疗策略,讨论海绵体神经损伤性ED治疗的基础及临床研究现状,既涉及神经营养因子、RhoA/ROCK抑制剂、亲免素配体、促红细胞生成素、干细胞治疗、基因治疗等传统策略,也包含富血小板血浆和低强度体外冲击波治疗等易于临床转化的新的治疗方式。本综述旨在为相关领域学者提供参考,以期开展更多具有较高临床转化意义的研究。     

海绵体注射尿激酶治疗阴茎异常勃起

阴茎异常勃起是指无任何性欲要求状态下所呈现的阴茎疼痛性持续性勃起。此症常需要紧急处理 ,延误治疗会导致永久性阴茎勃起功能障碍。现将我院近两年来收治 5例资料报告如下。1　一般资料本组 5例 ,2 4～ 3 3岁 ,平均 2 8岁。 5例中有 4例均为心理性阴茎勃起功能障碍 ,用罂粟碱与酚妥拉明注射于阴茎海绵体内 ,1例为自发性夜间勃起。发病后均于 6ｈ内就诊。2 　 方法与结果采用海绵体注射尿激酶法 ,将国产尿激酶1万Ｕ溶于生理盐水 6ｍｌ,注射于阴茎海绵体的两侧。注射后 2 0ｍｉｎ全部阴茎开始变软 ,勃起消失 ,无任何不适。随访半年无并发症…     

勃起功能障碍阴茎血流动力学研究

目的 探讨勃起功能障碍(erectile dysfunction,ED)的病因诊断。方法 130例ED患者通过阴茎海绵体内应用血管活性药物,进行阴茎海绵体血流动力学和海绵体造影检查。观察并记录阴茎一肱动脉血压指数(penile brachial index,PBI)、海绵体内压(intracavermous pressure,ICP)、维持灌流率(maintenance flow rate,MFR),海绵体内压跌差(pressure loss change,PLC)等项指标及阴茎静脉血管形态。结果 130例ED中有39例为静脉漏,其中15例为动脉血供不足伴静脉漏。海绵体造影显示28例为单纯背深静脉漏,其余11例为背深静脉复合阴茎脚静脉漏。结论 阴茎血流动力学检测可作为ED病因诊断的有效方法。     

Entubulization repair of severed cavernous nerves in the rat resulting in return of erectile function.

Erectile dysfunction is a significant complication of radical pelvic surgery in men. Using the rat as an experimental model, we investigated the feasibility of repairing surgically ablated cavernous nerves utilizing silastic tube nerve growth conduits filled with nerve growth enhancing media. Known fertile male Sprague-Dawley rats were randomly divided into four surgical groups consisting of nerve ablation, immediate nerve reconstruction utilizing the entubulization technique (two groups) and control. The nerve ablation group had five mm. sections of the cavernosal nerve excised bilaterally. The entubulization nerve graft group had five mm. sections of the cavernous nerve excised bilaterally, followed by immediate microsurgical reconstruction with a silastic nerve tube conduit filled with either Matrigel and heparin (MA) or Matrigel and heparin plus acidic fibroblast growth factor (MA/aFGF), interposed between the severed cavernous nerve stumps bilaterally. The control group underwent sham operations with the cavernous nerves being exposed only. Erectile function was evaluated at one, two, and four months postoperatively. Return of erectile function was defined as tumescence of the corporal bodies with application of direct electrical stimulation (four volts of five millisecond pulses at 20 Hertz) to the proximal cavernous nerves. The two and four month electrical stimulation studies resulted in tumescence from 50% and 58% of the entubulization nerve reconstructed nerves with MA/aFGF versus 29% and 30% for the MA only group and only 5% and 11% for the ablated group, respectively. We conclude that in this experimental model immediate nerve graft repair utilizing entubulization techniques with the addition of nerve growth enhancing media appears to be a successful method of salvaging erectile function when the cavernous nerves have been divided.     

Neuroimmunophilin ligands protect cavernous nerves after crush injury in the rat: new experimental paradigms

OBJECTIVES: We investigated the effects of the orally bioavailable non-immunosuppressive immunophilin ligand GPI 1046 (GPI) on erectile function and cavernous nerve (CN) histology following unilateral or bilateral crush injury (UCI, BCI, respectively) of the CNs. METHODS: Adult male Sprague-Dawley rats were administered GPI 15 mg/kg intraperitoneally (ip) or 30 mg/kg orally (po), FK506 1 mg/kg, ip, or vehicle controls for each route of administration just prior to UCI or BCI and daily up to 7 d following injury. At day 1 or 7 of treatment, erectile function induced by CN electrical stimulation was measured, and electron microscopic analysis of the injured CN was performed. RESULTS: Intraperitoneal administration of GPI to rats with injured CN protected erectile function, in a fashion similar to the prototypic immunophilin ligand FK506, compared with vehicle-treated animals (93%+/-9% vs. 70%+/-5% vs. 45%+/-1%, p<0.01, respectively). Oral administration of GPI elicited the same level of significant protection from CN injury. GPI administered po at 30 mg/kg/d, dosing either once daily or four times daily with 7.5 mg/kg, provided nearly complete protection of erectile function. In a more severe BCI model, po administration of GPI maintained erectile function at 24 h after CN injury. Ultrastructural analysis of injured CNs indicated that GPI administered at the time of CN injury prevents degeneration of about 83% of the unmyelinated axons at 7 d after CN injury. CONCLUSIONS: The orally administered immunophilin ligand GPI neuroprotects CNs and maintains erectile function in rats under various conditions of CN crush injury.     

自体隐静脉搭桥对离断海绵体神经的修复作用

目的探讨使用自体隐静脉搭桥修复离断海绵体神经(CN),恢复自主勃起功能的可行性。方法建立大鼠双侧CN离断并部分切除模型,取大鼠自体大隐静脉,利用显微外科技术桥接离断的CN,并术后每日腹腔注射生长激素400μg/kg体重,以假手术组和双侧CN离断组分别作为阳性和阴性对照。4个月后,阿朴吗啡试验评估大鼠的勃起功能;然后对勃起神经通路进行荧光金逆行追踪,观察CN的再生与再通情况。结果静脉搭桥组的勃起率达70%(7/10),明显高于CN离断组(0%),P<0.01;注入大鼠双侧阴茎海绵体荧光金5d后,静脉搭桥组大鼠盆神经节中发黄色荧光的神经细胞平均为(75.5±16.3)个,且较明亮,而CN离断组中只有(15.5±5.2)个,且很微弱。两者差异有统计学意义(P<0.01)。结论自体静脉搭桥结合使用生长激素修复离断缺损的CN,能够重建勃起神经通路,恢复一定程度的勃起功能。     

生殖股神经移植重建大鼠勃起神经通道

目的　探讨利用生殖股神经移植加神经生长强化介质修复损伤的阴茎海绵体神经,重建勃起神经通道的可行性。　方法　3月龄SD雄性大鼠54只,随机平均分成假手术对照组、双侧阴茎海绵体神经损伤组及神经移植加胰岛素样神经生长因子Ⅰ(IGF Ⅰ)组。术后1、3、6个月用阿朴吗啡试验评估各组动物勃起功能,并取阴茎干组织,采用NADPH d组化法了解nNOS阳性神经纤维的再生情况。　结果　术后1、3、6个月,假手术对照组均有正常阴茎勃起(勃起率100% ),神经切断组完全丧失勃起功能(勃起率0% );术后1个月神经移植组也丧失勃起功能(勃起率0% ),术后3、6个月勃起功能渐恢复(勃起率分别为50%和66. 7% ),两两比较差异有统计学意义(P<0. 05)。术后3、6个月,神经移植组nNOS 阳性神经纤维数显著增多,神经部分切断组的nNOS阳性神经纤维数和术后1个月相比无增多,两两比较差异有统计学意义(P<0. 002)。　结论　双侧阴茎海绵体神经损伤后,利用生殖股神经移植加IGF促进神经再生,是重建勃起神经通路,恢复大鼠勃起功能的一种有效方法。     

神经干细胞移植重建勃起功能的研究

目的 观察神经干细胞移植修复损伤的海绵体神经从而恢复勃起功能的可行性.方法 42只雄性SD大鼠(3～4个月龄和体质量300～400 g)随机分为假手术组、神经干细胞移植组和神经损伤组,每组14只.2、4个月后,海绵体神经电刺激检测大鼠阴茎勃起功能,免疫组织化学法检测海绵体内一氧化氮合酶(nNOS)阳性神经纤维.结果 2个月后3组大鼠对海绵体神经电刺激的勃起反应率分别为100%、0%和0%;3组海绵体内nNOS阳性神经纤维数目分别为98.5±9.2、22.5±3.5和25.7±5.1,后2组间差异无统计学意义(P>0.05).4个月后3组大鼠电刺激后勃起率分别为100%、57.14%和7.19%,后2组间差异有统计学意义(P<0.05);3组海绵体内nNOS阳性神经纤维数目分别为95.1±7.7、86.0±13.4、26.5±4.3,前2组间差异无统计学意义(P>0.05),后2组间差异有统计学意义(P<0.05).结论 神经干细胞移植是修复损伤的海绵体神经从而恢复勃起功能的一种有效方法.     

前列腺癌根治术后勃起功能障碍动物模型的建立

目的 对大鼠海绵体神经(CN)进行解剖并对其造成钳夹损伤,以建立前列腺癌根治术(RP)后勃起功能障碍(ED)的动物模型.方法 将36只雄性SD大鼠随机分为模型组、假手术组、正常组,术后4周通过阿朴吗啡(APO)实验及海绵体内压(ICP)/平均动脉压(MAP)测定、阴茎神经型一氧化氮合酶(nNOS)免疫组织化学检测以评估建立模型的效果.结果 术后4周3组大鼠的阴茎勃起率和平均勃起次数分别为0%和0次、100%(11/11)和(2.24±0.86)次、100%(12/12)和(2.39±0.92)次.模型组大鼠无明显勃起反应,假手术组、正常组可见明确勃起反应.电刺激盆腔星状神经节(MPG)前3组大鼠ICP/MAP分别为(0.13±0.04)、(0.10±0.03)、(0.12±0.03),电刺激MPG后分别为(0.12±0.05)、(0.57±0.08)、(0.58±0.06),电刺激MPG前3组ICP/MAP差异均无统计学意义(P＞0.05),模型组与假手术组、正常组的电刺激MPG后ICP/MAP差异有统计学意义(P＜0.05).3组大鼠阴茎nNOS阳性神经纤维数分别为(23.04±2.59)、(73.94±7.51)、(80.26±6.95),模型组大鼠阴茎nNOS阳性神经纤维数明显少于假手术组、正常组(P＜0.05).结论 大鼠CN结构与人类非常相似,CN钳夹损伤是建立RP术后ED模型的可靠的方法.

Abstract：

Objective To identify rat cavernous nerve (CN) and develop a rat model of erectile dysfunction (ED) after radical prostatectomy (RP) caused by injury of cavernous nerve.Methods Thirty-six male SD rats were were randomly divided into 3 groups:model group,sham-operation group and nomal group.Four weeks after surgery,rat models were evaluated by apomorphine test,ICP/MAP measurement and nNOS-positive nerve fibres in penis.Results The rats in model group had no erectilty in apomorphine test and electical stimulating MPG.The rats in sham-operation group and nomal group had erectility at the same conditions,accompanied with increased ICP/MAP in electrical stimulation ( P＜0.05 ).The nNOS-positive nerve fibres in model group ( 23.04 ± 2.59 ) were less than those in sham-operation group (73.94 ±7.51 ) and normal group (80.26 ±6.95 ).Conclusion Cavernous nerve in rats is highly similar to that in human beings.The rat model of erectile dysfunction after radical prostatectomy caused by cavernous nerve crush injury is reliable.     

Pentoxifylline promotes recovery of erectile function in a rat model of postprostatectomy erectile dysfunction

Background

Cavernous nerve (CN) injury during radical prostatectomy (RP) causes CN degeneration and secondary penile fibrosis and smooth muscle cell (SMC) apoptosis. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that further inhibits multiple cytokine pathways involved in nerve degeneration, apoptosis, and fibrosis.

Objectives

To evaluate whether PTX enhances erectile function in a rat model of CN injury.

Design, Setting and Interventions

Forty male Sprague-Dawley rats underwent CN crush injury and were randomized to oral gavage feeding of phosphate-buffered saline (vehicle) or PTX 25, PTX 50, or PTX 100 mg/kg per day. Ten animals underwent sham surgery and received vehicle treatment. Treatment continued for 28 d, followed by a wash-out period of 72 h. An additional eight rats underwent resection of the major pelvic ganglion (MPG) for tissue culture and examination of direct effects of PTX on neurite sprouting.

Measurements

Intracavernous pressure recording on CN electrostimulation, immunohistologic examination of the penis and the CN distal to the injury site, and length of neurite sprouts in MPG culture.

Results

Daily oral gavage feeding of PTX resulted in significant improvement of erectile function compared to vehicle treatment in all treated groups. After treatment with PTX 50 and PTX 100 mg/kg per day, the expression of neuronal nitric oxide synthase in the dorsal penile nerve was significantly higher than in vehicle-treated rats. Furthermore, PTX treatment prevented collagen deposition and SMC loss in the corpus cavernosum. In the CN, signs of Wallerian degeneration were ameliorated by PTX treatment. MPG culture in medium containing PTX resulted in a significant increase of neurite length.

Conclusions

PTX treatment following CN injury in rats improved erectile recovery, enhanced nerve regeneration, and preserved the corpus cavernosum microarchitecture. The clinical availability of this compound merits application in penile rehabilitation studies following RP in the near future.     

Both immediate and delayed intracavernous injection of autologous adipose-derived stromal vascular fraction enhances recovery of erectile function in a rat model of cavernous nerve injury

Background

Intracavernous injection of cultured adipose-derived stem cells (ADSCs) effectively restores erectile function in cavernous nerve (CN)–injured rats when administered at the time of injury. However, culturing exposes ADSCs to the risk of contamination and dedifferentiation.

Objective

Explore the effect of uncultured autologous adipose-derived stromal vascular fraction (SVF) on improving erectile function in a rat model of CN injury when administered at the time of injury or 4 wk after injury.

Design, setting, and participants

Eighty-nine male Sprague Dawley rats were randomly divided into four groups. CN injury or sham surgery was performed at the start of the study, and rats were treated with either SVF or vehicle. Functional testing and histologic analysis were performed 12 wk after CN crush or sham surgery.

Intervention

We used intracavernous injection of saline immediately after CN crush (n = 23), intracavernous injection of SVF immediately after CN crush (n = 17), intracavernous injection of SVF 4 wk after CN crush (n = 23), or sham surgery (n = 26).

Outcome measurements and statistical analysis

We studied intracavernous pressure (ICP) response to CN electrostimulation and performed histologic examination of midpenile cross-sections. Data were analyzed using one-way analysis of variance followed by the Tukey-Kramer test.

Results and limitations

Both immediate and delayed treatment with SVF resulted in a significantly increased ICP-to-mean arterial pressure ratio compared with the vehicle-treated group. Both immediate and delayed treatment with SVF significantly increased expression of neuronal nitric oxide synthase and neurofilament in dorsal penile nerves compared to the vehicle group. Furthermore, the smooth muscle-to-collagen ratio within the corpus cavernosum was significantly improved in both of the SVF groups compared to vehicle-treated rats. The main limitation of the study is the lack of determination of the SVF components.

Conclusions

Uncultured autologous SVF injected immediately or 4 wk after CN crush improved erectile function, promoted nerve regeneration, and prevented fibrosis of the corpus cavernosum following CN injury.     

Single potential analysis of cavernous electrical activity

Summary Recording of cavernous electric activity was performed in 178 patients with erectile dysfunction and in 37 normal patients. In 34/37 normal patients, potentials of a uniform shape were recorded during flaccidity: At cut-off frequences of 0.5–500 Hz, the length was 8–18 (mean 12.8, SD 2.8), the amplitude 250–750 (mean 444, SD 109) V, and the polyphasity 8–22 (mean 13.8, SD 3.3). In impotent patients with upper motor neuron lesions or peripheral lesions, specific types of potentials were observed. In 11/14 impotent patients with insulin-dependent diabetes for over 20 years and clinical findings of cavernous myopathy, potentials showed low amplitude, irregular shape, and slow depolarizations. In 51% of the consecutive impotent patients, abnormal findings of cavernous electric activity were recorded. Our clinical study suggests that single potential analysis of cavernous electric activity (SPACE) may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.This study was supported by a grant of the Deutsche Forschungsgemeinschaft (Sti 96/2-1)Part of this paper was presented at the 10th Symposium of the Association for Experimental Urology of the German Urological Society, June 21–23, 1990, Munich, FRG     

经尿道前列腺电切术对勃起功能影响的研究

目的:分析经尿道前列腺电切术(TURP)对勃起功能的影响程度及引起术后勃起功能障碍的各种 因素。方法:随访257例行TURP术患者,按年龄、前列腺切除重量、术前性功能状况、术后是否有低钠血症和术 中前列腺包膜是否穿破五个因素分别比较其作用下的术前术后性功能改变情况。并采用电切术切除犬前列腺组 织,观察其电切术后前列腺损伤深度及标志勃起神经功能的指标(一氧化氮活性),评估电切术对勃起神经损伤程 度的影响。结果:术中前列腺切除重量大小与术后是否有低钠血症发生对TURP术后勃起功能障碍的发生无明 显关系(P>0.05)。>65岁者与≤65岁者、术前性功能不完全者与术前性功能完全者、术中穿破前列腺包膜与 包膜完整者的三因素中,前者术后勃起功能障碍发生率均比后者高(P<0.05)。实验研究显示电切术损伤仅局 限于前列腺本身,最深仅为1.6mm。阴茎海绵体一氧化氮活性测定,术前术后差别无统计学意义。结论:年龄、 术前性功能状况、术中是否穿破前列腺包膜三因素对TURP术后勃起功能障碍影响明显。实验研究显示电切术 损伤仅局限于前列腺本身。经尿道前列腺电切术只要操作规范,手术本身并不引起术后勃起功能障碍。