Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Sex Med. 2018 Mar;15(3):304-313. doi: 10.1016/j.jsxm.2018.01.011.
Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases.
To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI).
Rats underwent BCNI or a sham operation and were treated with vehicle or β-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry.
Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content.
After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. β-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content.
LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction.
This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation.
CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313.
海绵体神经损伤（CNI）导致海绵体平滑肌细胞（SMCs）纤维化和丢失，导致勃起功能障碍，而赖氨酰氧化酶（LOX）的激活被发现在纤维性疾病中起着重要作用。
评估 LOX 在双侧海绵体神经损伤（BCNI）后的阴茎纤维化中的作用。
大鼠接受 BCNI 或假手术，并接受载体或β-氨基丙腈（一种特定的 LOX 活性抑制剂）治疗。BCNI 后 30 天，在进行阴茎组织采集之前，对大鼠进行勃起功能测试。通过实时定量聚合酶链反应和 Western blot 评估海绵体中 LOX 和细胞外基质成分的表达水平，包括基质金属蛋白酶（MMPs）、金属蛋白酶组织抑制剂（TIMPs）、纤维连接蛋白（FN）、胶原（COL）I 和 COL IV。通过 Masson 三色染色评估阴茎纤维化。通过免疫组织化学评估 LOX 和海绵体 SMC 含量的定位。
海绵体内压与平均动脉血压的比值；LOX、MMPs、TIMPs、COL I、COL IV 和 FN 表达；阴茎纤维化；阴茎 SMC 含量。
CNI 诱导海绵体组织中 LOX 过度激活，LOX 抑制可能是预防 CNI 诱导的勃起功能障碍进展的一种有前途的策略。
