Xu Y, Xin H, Wu Y, Guan R, Lei H, Fu X, Xin Z, Yang Y
Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing, China.
Department of Ophthalmology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China.
Andrology. 2017 May;5(3):598-605. doi: 10.1111/andr.12341. Epub 2017 Mar 10.
The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis. Forty-eight rats of bilateral cavernous nerves injury were randomized equally into gavage feeding of vehicle, sildenafil (10 mg/kg), icariin (1.5 mg/kg) and sildenafil + icariin, respectively. Twelve sham-operated rats served as control. The intracavernous pressure and mean arterial pressure was measured and mid-penile cross sections were histologically examined 5 weeks after surgery. Western blotting of cavernous tissue protein was also performed. Animals treated with sildenafil + icariin had significantly higher mean intracavernous pressure/mean arterial pressure ratio relative to other rats with bilateral cavernous nerves injury (p < 0.05). The circumference and mean cross-sectional area of the paired corpus cavernosum were effectively preserved in the sildenafil + icariin. Treatment with sildenafil + icariin significantly increased the cavernous cyclic guanosine monophosphate concentration compared with the icariin group (p < 0.05). In addition, the numbers of neuronal nitric oxide synthase-positive nerves and 5-ethynyl-2-deoxyuridine-positive cells co-expressing S100 in the icariin-treated groups were greater compared with the bilateral cavernous nerves injury control group (p < 0.05). These data suggest that the combined use of icariin and daily sildenafil holds promise as a potential therapy for neurogenic erectile dysfunction in the future. The underlying mechanisms appears to involve two aspects: (i) icariin promotes differentiation of endogenous stem cells to Schwann cells, which help to repair the damaged neural pathway for erection; (ii) on this basis, sildenafil can further improve penile engorgement through the cyclic guanosine monophosphate-dependent smooth muscle relaxation.
常用的5型磷酸二酯酶抑制剂在根治性前列腺切除术后并不能带来令人满意的阴茎勃起，主要原因是受损海绵体神经产生的一氧化氮不足。本研究的目的是评估淫羊藿苷联合每日服用西地那非对双侧海绵体神经损伤大鼠模型神经源性勃起功能障碍和阴茎萎缩的疗效及机制。60只雄性Sprague-Dawley大鼠在出生后第1天注射5-乙炔基-2-脱氧尿苷（50mg/kg），用于追踪阴茎内的内源性干细胞。48只双侧海绵体神经损伤的大鼠被随机等分为分别灌胃给予赋形剂、西地那非（10mg/kg）、淫羊藿苷（1.5mg/kg）以及西地那非+淫羊藿苷。12只假手术大鼠作为对照。术后5周测量海绵体内压和平均动脉压，并对阴茎中段横截面进行组织学检查。还对海绵体组织蛋白进行了蛋白质印迹分析。与其他双侧海绵体神经损伤的大鼠相比，接受西地那非+淫羊藿苷治疗的动物的平均海绵体内压/平均动脉压比值显著更高（p<0.05）。西地那非+淫羊藿苷有效地保留了成对海绵体的周长和平均横截面积。与淫羊藿苷组相比，西地那非+淫羊藿苷治疗显著提高了海绵体环磷酸鸟苷浓度（p<0.05）。此外，与双侧海绵体神经损伤对照组相比，淫羊藿苷治疗组中共同表达S100的神经元型一氧化氮合酶阳性神经和5-乙炔基-2-脱氧尿苷阳性细胞的数量更多（p<0.05）。这些数据表明，淫羊藿苷与每日服用西地那非联合使用有望在未来成为治疗神经源性勃起功能障碍的潜在疗法。其潜在机制似乎涉及两个方面：（i）淫羊藿苷促进内源性干细胞向雪旺细胞分化，这有助于修复受损的勃起神经通路；（ii）在此基础上，西地那非可通过环磷酸鸟苷依赖性平滑肌舒张进一步改善阴茎充血。
