Objective      To investigate the role of endosplasmic reticulum stress (ERS) in protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis (IC)

and the potential therapeutic value of 4-phenylbutyric acid (4-PBA) in rats.       Methods      Forty-five female Sprague-Dawley rats were randomly divided into control group (C group)

IC group and IC+4-PBA group

with 15 rats in each group. IC model was established with PS/LPS infusion in bladder

while saline infusion was adopted in the control rats. The rats in the IC+4-PBA group received the same bladder infusion as the rats in the IC group

and 4-PBA solution was administered intragastrically once a day. In 5 d later

ERS biomarker (GRP78)

autophagy biomarkers (LC3A/B

Beclin1) and autophagy flux biomarker (P62) were assessed by Western blotting. Immunofluorescence staining of LC3A/B was conducted. The histopathologic changes of the bladder were observed by HE staining

and urination function was evaluated by urodynamic test.       Results      In the IC group

GRP78

LC3A/B

Beclin1 and P62 were increased as compared with the C group (P0.05)

and after 4-PBA was used to inhibit the ERS

these biomarkers were decreased. Immunofluorescence staining results revealed lower LC3A/B expression in the IC+4-PBA group than in the IC group and higher expression than in the C group (P0.05). HE staining results showed that the bladder epithelial tissue integrity

inflammatory cell infiltration and tissue edema degree were improved significantly in the IC+4-PBA group. As for bladder urination function

compared with the IC group

the bladder urination frequency was decreased significantly and the urination interval was significantly prolonged in the IC+4-PBA group.       Conclusion      4-PBA down-regulates the bladder excitation and protects the bladder function by inhibiting the ERS and restoring the autophagy flux in PS/LPS-induced IC.