Relaxin-2 Prevents Erectile Dysfunction by Cavernous Nerve, Endothelial and Histopathological Protection Effects in Rats with Bilateral Cavernous Nerve Injury

Kang Liu; Taotao Sun; Wenchao Xu; Jingyu Song; Yinwei Chen; Yajun Ruan; Hao Li; Kai Cui; Yan Zhang; Yuhong Feng; Jiancheng Pan; Enli Liang; Zhongcheng Xin; Tao Wang; Shaogang Wang; Jihong Liu; Yang Luan

doi:10.5534/wjmh.220003

Relaxin-2 Prevents Erectile Dysfunction by Cavernous Nerve, Endothelial and Histopathological Protection Effects in Rats with Bilateral Cavernous Nerve Injury

World J Mens Health. 2023 Apr;41(2):434-445. doi: 10.5534/wjmh.220003. Epub 2022 Jul 14.

Authors

Kang Liu^{1

2}, Taotao Sun^{1

2}, Wenchao Xu^{1

2}, Jingyu Song^{1

2}, Yinwei Chen^{1

2}, Yajun Ruan^{1

2}, Hao Li^{1

2}, Kai Cui^{1

2}, Yan Zhang^{1

2}, Yuhong Feng³, Jiancheng Pan³, Enli Liang³, Zhongcheng Xin³, Tao Wang^{1

2}, Shaogang Wang^{1

2}, Jihong Liu^{1

2}, Yang Luan^{1

4}

Affiliations

¹ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
³ Male Reproductive and Sexual Medicine, Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
⁴ Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. yangluan@tjh.tjmu.edu.cn.

Abstract

Purpose: 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).

Materials and methods: 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.

Results: 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 via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3.

Conclusions: RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Keywords: Apoptosis; Erectile dysfunction; Fibrosis; Nerve; Penis; Relaxin.

Abstract

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