Liu Kang, Sun Taotao, Xu Wenchao, Song Jingyu, Chen Yinwei, Ruan Yajun, Li Hao, Cui Kai, Zhang Yan, Feng Yuhong, Pan Jiancheng, Liang Enli, Xin Zhongcheng, Wang Tao, Wang Shaogang, Liu Jihong, Luan Yang
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
World J Mens Health. 2023 Apr;41(2):434-445. doi: 10.5534/wjmh.220003. Epub 2022 Jul 14.
Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI).
The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation.
Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3.
RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.
海绵体神经损伤所致勃起功能障碍（ED）是根治性前列腺切除术后患者中发生率较高的难治性并发症。研究表明，松弛素-2（RLX-2）在多种疾病中发挥着内皮保护、血管舒张、抗纤维化和神经保护的重要作用。然而，阴茎海绵体勃起是否能从RLX-2中获益尚不清楚。本实验旨在探讨RLX-2对双侧海绵体神经损伤（BCNI）大鼠勃起功能障碍的影响。
将大鼠分为三组：假手术组行假手术，BCNI+RLX组或BCNI组行双侧海绵体神经挤压术，然后分别用皮下植入式微型泵连续给药4周，随机给予RLX-2（0.4mg/kg/d）或生理盐水。然后，通过海绵体神经电刺激评估勃起功能。收集海绵体神经和阴茎组织进行组织学评估。
RLX-2治疗后，BCNI大鼠的勃起功能得到部分改善。与假手术大鼠相比，BCNI组松弛素家族肽受体（RXFP）1、p-AKT/AKT、p-eNOS/eNOS比值的表达较低，但RLX-2可部分逆转这些变化。组织学上，与BCNI组相比，BCNI+RLX组对阴茎组织的神经丝、神经元胶质抗原2和海绵体神经的nNOS的保存有显著影响。RLX-2可抑制BCNI诱导的海绵体纤维化和凋亡水平，调节TGFβ1-Smad2/3-CTGF途径以及Bax/Bcl-2比值、caspase3的表达。
RLX-2可通过保护海绵体神经和内皮功能，抑制海绵体纤维化和凋亡，通过RXFP1和AKT/eNOS途径改善BCNI大鼠的勃起功能。我们的研究结果可能为难治性BCNI所致ED提供一种有前景的治疗方法。
