4-PBA inhibits endoplasmic reticulum stress to improve autophagic flux in the treatment of protamine/lipopolysaccharide-induced interstitial cystitis in rats

Abstract Interstitial cystitis (IC) has severe clinical symptoms with unclear mechanism. The continuous inflammatory response of the bladder is the basis of its pathogenesis. Endoplasmic reticulum stress (ERS) is involved in the regulation and development of various inflammatory diseases. And autophagy plays an important role in IC. In this study, we mainly focus on the therapeutic effect of endoplasmic reticulum stress and autophagy on protamine/lipopolysaccharide-induced interstitial cystitis. Female Sprague–Dawley rats were randomized into three experimental groupsas follows: sham controls(N), IC alone, and IC+4-PBA.Rats in group IC received 10 mg/ml PS in the urinary bladder, followed by 2 mg/ml LPS instillation after 30 minutes, IC +4-PBA group SD rats received 4-PBA solution administered intragastrically once a day for 5days.ERS biomarker (GRP78), autophagy-related proteins (LC3I/II, and Beclin1), autophagic flux biomarker (P62), inflammatory biomarkers (IL-6, TNF-a, NF-kB) , apoptotic biomarkers (Caspase 3, Bax), anti-apoptotic biomarkers (Bcl-2) and oxidative stress biomarkers (HO-1 , NQO-1)revealed significantly different results among the groups. The histological score and mast cell count demonstrated most severe in the IC group than those in the IC+USC group. TUNEL assay examined the level of apoptosis in IC group was higher than in the IC+USC group. The bladder micturition function was significantly improved with4-PBA treatment.4-PBA inhibits ERS to recover autophagic flux, and then to suppress the bladder oxidative stress, the inflammatory reaction and apoptosis, finally improve the bladder urinary function in PS/LPS induced IC.