Prostaglandin E2 receptor 4 receptor antagonist vs.sodium hyaluronate for hyaluronidase-induced interstitial cystitis in rats

Abstract

Objective To compare the effects of prostaglandin E2 receptor 4(EP4)receptor antagonist vs.sodium hyaluronate on the hyaluronidase-induced interstitial cystitis in rats. Methods Fifty Sprague-Dawley rats were randomly divided into control group(15 rats,intravesical normal saline), model group(15 rats,intravesical hyaluronidase),antagonist group(10 rats,intraperitoneal AH23848),and mucosa protection group(10 rats,intraperitoneal hyaluronic acid).The rat interstitial cystitis models were created by long-term (1 month)intermittent intravesical hyaluronidase(4 g/L).Voiding patterns were investigated by cystometry. Rat bladder strips were used to examine bladder tension in vitro.The mRNA levels of interleukin-6 and interleukin-1 beta were analyzed by real-time reverse transcription polymerase chain reaction.The protein levels of EP4 and substance P in the bladder were determined by immunohistochemistry. Results As compared with control group, the intercontraction intervals[(145. 62±44. 96)s]and bladder capacity[(0. 40 ±0. 07) ml] were significantly decreased, and the mRNA levels of interleukin(IL)-6 and IL-1β, the protein levels of EP4 receptor and substance P were significantly increased in model group(all P<0. 05). After administration of EP4 antagonist AH23848 and sodium hyaluronate, the intercontraction intervals and bladder capacity were significantly increased, and the mRNA levels of IL-6 as well as IL-1βwere significantly decreased(all P< 0. 05).AH23848 showed a better effect on increasing the intercontraction intervals[(427. 52±54. 24)s] and bladder capacity[(1. 19±0. 09) ml] than sodium hyaluronate. AH23848 could also significantly decrease the expression of substance Pin the bladder, while sodium hyaluronate had no such effect.Furthermore, AH23848 could relax the KCl-induced contraction of bladder strips from rats induced by hyaluronidase[inhibition with(19. 75±3. 59)%,P< 0. 05]. Conclusion As compared with sodium hyaluronate, EP4 receptor antagonist AH23848 could relax KCl-induced contraction of bladder strips, improve the frequent micturition of hyaluronidase-induced rats, and ameliorate the bladder pain.Consequently,its antagonist may act as a new therapeutic target for interstitial cystitis/bladder pain syndrome(IC/BPS). Key words: Prostaglandin E2 receptor 4; Sodium hyaluronate; Interstitial cystitis