The Involvement of the H2S/CBS/CSE Signaling Pathway in Bladder Pain Model Inflammation and Its Mechanisms Affecting Voiding Function

Abstract

Background: Interstitial Cystitis (IC), also known as bladder pain syndrome (BPS), is a chronic urinary system disorder characterized by pelvic pain and urinary discomfort. The specific mechanisms underlying IC/BPS are yet to be fully understood. This study aimed to explore the role of the hydrogen sulfide (H₂S)/cystathionine β-synthase (CBS)/cystathionine γ-lyase (CSE) signaling pathway in the IC/BPS model and its impact on urinary function mechanisms. Method: Sprague-Dawley (SD) rats (n = 100) were randomly assigned into four groups: a control group (CG), a model group (MG), an inhibition group (IG), and an activation group (AG), with 25 rats in each group. The MG group was treated with acetylcholine to establish a bladder pain model (BPM), while the CG group received an equivalent quantity of saline treatment. Furthermore, the IG group was treated with H₂S/CBS/CSE signaling pathway (SPW) inhibitors, while the AG group was intraperitoneally administered with H₂S/CBS/CSE SPW activators. All rats were consistently fed, and their voiding behavior was observed, subsequently, their voiding function was evaluated after one day. Furthermore, rats were euthanized three days after treatments, and bladder tissue was surgically excised. Additionally, the levels of inflammatory factors and the activities of related pathway enzymes were assessed in the bladder tissues. Results: Compared to the CG group, both the MG and IG groups exhibited a significant increase in Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6) levels, as well as in bladder pressure (p < 0.01). However, urinary flow rate (UFR) and the activity of ion-channels (Na⁺, K⁺, and Na⁺/Ca²⁺) related enzymes were significantly decreased (p < 0.01) in these groups. In the AG, the bladder tissue had lower levels of IL-1β, TNF-α, IL-6, and bladder pressure compared to the CG group (p < 0.05), while UFR and the activity of ion-channels (Na⁺, K⁺, and Na⁺/Ca²⁺) related enzymes were significantly higher compared to the CG group (p < 0.05). Conclusion: The H₂S/CBS/CSE SPW alleviated bladder pain and improved voiding function in rats by reducing the levels of inflammatory factors, attenuating inflammatory responses, and regulating bladder contraction and relaxation.