Department of Urology, Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
Sex Med Rev. 2018 Oct;6(4):572-582. doi: 10.1016/j.sxmr.2018.02.007. Epub 2018 Apr 7.
Cavernosal fibrosis is an important pathologic condition leading to erectile dysfunction (ED). The etiologies of cavernosal fibrosis include aging, diabetes mellitus, castration, cavernosal nerve injury during radical prostatectomy, hypertension, and Peyronie disease.
To summarize published studies investigating suppression of cavernosal fibrosis in rat models of ED of various etiologies.
A literature search was conducted using PubMed. Relevant studies were identified using search terms such as erectile dysfunction, penis, fibrosis, and rat models.
We reviewed representative literature studies on the mechanisms and suppression of cavernosal fibrosis in rat models of ED.
The underlying mechanisms and potential therapeutic strategies suggested thus far for cavernosal fibrosis in rat models of ED were as follows. For age-related ED involving oxidative stress and tumor growth factor-β1 (TGF-β1)-driven pathways such as RhoA-ROCK1-LIMK2-cofilin or p42-44 and mitogen-activated protein kinase, proposed therapeutic strategies included phosphodiesterase type 5 inhibitors (PDE5Is), kallikrein-kinin system stimulators, and calorie restriction. For diabetes-related ED involving angiotensin-II- and TGF-β1-driven Smad and non-Smad pathways, TGF-β1-Wnt10b, and histone deacetylase (HDAC)-TGF-β1 pathways, positive therapeutic results were obtained with PDE5Is, TGF-β1 antagonists, HDAC inhibitors, antioxidants, sphingosine-1-phosphate receptor modulators (fingolimod), angiotensin-II antagonists, stem cell therapy, and antidiabetic drugs. For cavernosal nerve injury-associated ED involving TGF-β1-driven pathways (Smad or RhoA-ROCK1-LIMK2-cofilin), Sonic hedgehog signaling, angiotensin-II-Smad, and HDAC4-TGF-β1-Smad signaling triggered by cavernosal hypoxia, PDE5Is, angiotensin-II antagonists, stem cell therapy, HDAC inhibitors, Sonic hedgehog administration, ROCK inhibitors, and LIMK2 inhibitors have shown positive results. For testosterone deficiency-associated ED, TGF-β1-driven pathways were found to be responsive to testosterone supplementation. For hypertensive ED, positive therapeutic results were obtained with angiotensin-II antagonists. For Peyronie disease involving TGF-β1 or myostatin signaling, proposed therapeutic strategies included intra-tunical injection of TGF-β receptor inhibitors or adipose tissue-derived stem cells and HDAC2 small hairpin RNA.
Several signaling pathways appear to be responsible for the development of cavernosal fibrosis related to ED of various etiologies. Some therapeutic success has been achieved in animal models, but further research focusing on mechanism-specific targeted therapies is needed. Cho MC, Song WH, Paick J-S. Suppression of Cavernosal Fibrosis in a Rat Model. Sex Med Rev 2018;6:572-582.
海绵体纤维化是导致勃起功能障碍（ED）的重要病理状态。海绵体纤维化的病因包括衰老、糖尿病、去势、根治性前列腺切除术时的海绵体神经损伤、高血压和 Peyronie 病。
总结各种病因 ED 大鼠模型中海绵体纤维化抑制的已发表研究。
使用 PubMed 进行文献检索。使用“勃起功能障碍、阴茎、纤维化和大鼠模型”等搜索词来确定相关研究。
我们回顾了关于 ED 大鼠模型中海绵体纤维化的机制和抑制的代表性文献研究。
迄今为止，针对 ED 大鼠模型中海绵体纤维化的潜在机制和潜在治疗策略如下。对于涉及氧化应激和转化生长因子-β1（TGF-β1）驱动途径的与年龄相关的 ED，如 RhoA-ROCK1-LIMK2-肌动蛋白或 p42-44 和丝裂原激活蛋白激酶，提出的治疗策略包括磷酸二酯酶 5 抑制剂（PDE5Is）、激肽释放酶-激肽系统激动剂和热量限制。对于涉及血管紧张素-II 和 TGF-β1 驱动的 Smad 和非 Smad 途径、TGF-β1-Wnt10b 和组蛋白去乙酰化酶（HDAC）-TGF-β1 途径的糖尿病相关 ED，PDE5Is、TGF-β1 拮抗剂、HDAC 抑制剂、抗氧化剂、鞘氨醇 1-磷酸受体调节剂（fingolimod）、血管紧张素-II 拮抗剂、干细胞治疗和抗糖尿病药物均取得了积极的治疗效果。对于海绵体神经损伤相关的 ED，涉及 TGF-β1 驱动途径（Smad 或 RhoA-ROCK1-LIMK2-肌动蛋白）、Sonic Hedgehog 信号、血管紧张素-II-Smad 和由海绵体缺氧触发的 HDAC4-TGF-β1-Smad 信号，PDE5Is、血管紧张素-II 拮抗剂、干细胞治疗、HDAC 抑制剂、Sonic Hedgehog 给药、ROCK 抑制剂和 LIMK2 抑制剂已显示出积极的结果。对于与睾丸激素缺乏相关的 ED，发现 TGF-β1 驱动途径对睾丸激素补充有反应。对于高血压性 ED，血管紧张素-II 拮抗剂取得了积极的治疗效果。对于涉及 TGF-β1 或肌生成素信号的 Peyronie 病，提出的治疗策略包括海绵体内注射 TGF-β 受体抑制剂或脂肪组织来源的干细胞和 HDAC2 短发夹 RNA。
一些信号通路似乎与各种病因引起的 ED 相关的海绵体纤维化的发展有关。在动物模型中已取得一些治疗成功，但需要进一步研究针对特定机制的靶向治疗。
