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Updated: Jun 10, 2025
Cavernous Nerve Stimulation and Recording of Intracavernous Pressure in a Rat
Published on: April 23, 2018
Mechanism of denervation muscle atrophy mediated by Ach/p38/MAPK pathway in rats with erectile dysfunction caused by
Huang Wen Jie1, Wang Jie2, Ma Jianxiong3
1Department of Urology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, China.
Background:
Peripheral nerve injury can result in penile cavernosal denervation muscle atrophy, a primary factor in nerve injury erectile dysfunction (NED). While acetylcholine (Ach) is integral to erectile function, its role and mechanisms in NED need further exploration.
Objective:
To investigate the inhibition of CCMSCs Apoptosis and Protein Degradation Pathway by Ach in NED rat model.
Methods:
We investigated changes in Ach secretion and receptor expression in an NED rat model, followed by the evaluation of apoptosis and ubiquitin proteasome activation in hypoxic Cavernous smooth muscle cells (CCMSCs) and their co-cultures with Schwann cells (SWCs), under Ach influence. Further, key pathways in NED were identified via high-throughput sequencing, focusing on the p38/MAPK signaling pathway. We examined gene alterations related to this pathway using hypoxic cell models and employed p38 inhibitors to verify protein changes. Our findings in vitro were then confirmed in the NED rat model.
Results:
Nerve injury led to reduced Ach receptors and associated gene expression. Experimentally, Ach was shown to counteract CCMSC apoptosis and muscle protein degradation via the p38/MAPK pathway. Inhibition of the Ach degradation pathway demonstrated a capacity to slow NED progression in vivo.
Discussion And Conclusion:
Activation of Ach receptors may decelerate denervation-induced cavernosal muscle atrophy, suggesting a potential therapeutic approach for NED. This study highlights the crucial role of the Ach/p38/MAPK axis in the pathophysiology of penis smooth muscle atrophy and its broader implications in managing NED and male erectile dysfunction.
