Sturny Mikael, Karakus Serkan, Fraga-Silva Rodrigo, Stergiopulos Nikolaos, Burnett Arthur L
Ecole Polytechnique Fédérale de Lausanne, Department of Bioengineering, Laboratory of Hemodynamics and Cardiovascular Technology, Lausanne, Switzerland; Johns Hopkins School of Medicine, The James Buchanan Brady Urological Institute and Department of Urology, Baltimore, MD, USA.
Johns Hopkins School of Medicine, The James Buchanan Brady Urological Institute and Department of Urology, Baltimore, MD, USA.
J Sex Med. 2022 May;19(5):686-696. doi: 10.1016/j.jsxm.2022.02.004. Epub 2022 Mar 11.
Neurogenic erectile dysfunction (ED) following radical prostatectomy (RP) is a frequent complication often leading to erectile tissue remodeling and permanent ED. Low-intensity electrostimulation (LIES) has been shown to enhance peripheral nerve regeneration, however, its application on cavernous nerves (CN) has never been investigated.
To investigate whether LIES enhances CN regeneration, improves erectile function (EF) recovery, and prevents corpora cavernosal remodeling after CN injury, which is a principal factor for ED following RP.
Adult male Sprague-Dawley rats were divided into Sham, Bilateral Cavernous Nerve Injury (BCNI), and BCNI + LIES (1V, 0.1ms, 12Hz, 1h/day). After 7days, EF was assessed (ICP measurement). Penes and CN were collected for molecular analyses of TGF-β1, Il-6, CRP, eNOS, ERK and AKT protein levels in corpus cavernosum (CC), and immunohistological analysis of DHE, total collagen and α-SMA in CC and S-100, Tub-III, DAPI, TUNEL, and nNOS in CN.
Effects of LIES on EF, erectile tissue remodeling and CN structure.
EF was decreased (P < .05) 7 days after BCNI and increased (P < .05) by LIES. Intracavernosal reactive oxygen species (DHE) was increased (P < .05) after BCNI and normalized by LIES. Protein expressions of TGF-β1, IL-6, and CRP were increased in the penis (P < .05) after BCNI and normalized by LIES. The α-SMA and/or total collagen ratio was decreased (P < .05) after BCNI in the penis and normalized by LIES. Protein expression ratio of p-ERK/ERK and p-AKT/AKT did not change after BCNI but increased (P < .05) in LIES group. Myelination and number of nNOS positive cells in the CN were decreased (P < .05) after BCNI and normalized by LIES. The number of apoptotic nerve cells within the dorsal penile nerve was increased (P < .05) after BCNI and decreased (P < .05) by LIES compared to the BCNI group. There were no differences in eNOS expression in the penis between study groups.
LIES may offer a potential new tool for penile rehabilitation and ED management following RP, potentially enhancing EF recovery and minimizing the side effects of this surgery.
STRENGTHS & LIMITATIONS: This study provides evidence of the protective effect of LIES on EF and tissue remodeling following CN injury; nevertheless, this study has been conducted on animals and the translation to humans remains to be demonstrated. Further research to identify the underlying mechanisms of action is required.
This study demonstrates that LIES of the CN after CN injury protects CN structure, enhances EF recovery, and prevents corpora cavernosal remodeling. Sturny M, Karakus S, Fraga-Silva R, et al. Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med 2022;19:686-696.
根治性前列腺切除术后（RP）的神经源性勃起功能障碍（ED）是一种常见并发症，常导致勃起组织重塑和永久性ED。低强度电刺激（LIES）已被证明可促进周围神经再生，然而，其在海绵体神经（CN）上的应用从未被研究过。
研究LIES是否能促进CN再生、改善勃起功能（EF）恢复，并预防CN损伤后海绵体重塑，而CN损伤是RP后ED的主要因素。
将成年雄性Sprague-Dawley大鼠分为假手术组、双侧海绵体神经损伤组（BCNI）和BCNI + LIES组（1V，0.1ms，12Hz，每天1小时）。7天后，评估EF（通过测量海绵体内压）。收集阴茎和CN，用于分析海绵体（CC）中转化生长因子-β1、白细胞介素-6、C反应蛋白、内皮型一氧化氮合酶、细胞外信号调节激酶和蛋白激酶B的蛋白水平，并对CC中的脱氢表雄酮、总胶原蛋白和α-平滑肌肌动蛋白进行免疫组织学分析，对CN中的S-100、微管蛋白-III、4',6-二脒基-2-苯基吲哚、末端脱氧核苷酸转移酶介导的缺口末端标记和神经元型一氧化氮合酶进行免疫组织学分析。
BCNI后7天EF降低（P < 0.05），LIES使其升高（P < 0.05）。BCNI后海绵体内活性氧（脱氢表雄酮）增加（P < 0.05），LIES使其恢复正常。BCNI后阴茎中转化生长因子-β1、白细胞介素-6和C反应蛋白的蛋白表达增加（P < 0.05），LIES使其恢复正常。BCNI后阴茎中α-平滑肌肌动蛋白和/或总胶原蛋白比例降低（P < 0.05），LIES使其恢复正常。BCNI后p-ERK/ERK和p-AKT/AKT的蛋白表达比例未改变，但LIES组升高（P < 0.05）。BCNI后CN中的髓鞘形成和神经元型一氧化氮合酶阳性细胞数量减少（P < 0.05），LIES使其恢复正常。与BCNI组相比，BCNI后阴茎背神经内凋亡神经细胞数量增加（P < 0.05），LIES使其减少（P < 0.05）。研究组之间阴茎中内皮型一氧化氮合酶表达无差异。
LIES可能为RP后的阴茎康复和ED管理提供一种潜在的新工具，可能增强EF恢复并最小化该手术的副作用。
本研究提供了LIES对CN损伤后EF和组织重塑具有保护作用的证据；然而，本研究是在动物身上进行的，向人类的转化仍有待证明。需要进一步研究以确定其潜在的作用机制。
本研究表明，CN损伤后对CN进行LIES可保护CN结构，增强EF恢复，并预防海绵体重塑。Sturny M, Karakus S, Fraga-Silva R等。低强度电刺激增强海绵体神经损伤大鼠模型中的神经再生并改善勃起功能。《性医学杂志》2022；19：686 - 696。
