The potential mechanism of treating IC/BPS with hyperbaric oxygen by reducing vascular endothelial growth inhibitor and hypoxia-inducible factor-1α

Abstract

Background/aim: To investigate the roles of vascular endothelial growth inhibitor (VEGI) and hypoxia-inducible factor-1α (HIF-1α) in the treatment of refractory interstitial cystitis/bladder pain syndrome (IC/BPS) with hyperbaric oxygen (HBO).

Materials and methods: A total of 38 patients were included. They were assessed before and 6 months after HBO treatment. Three-day voiding diaries were recorded, and O'leary-Sant scores, visual analog scale (VAS) scores, quality of life (QoL) scores, pelvic pain, and urgency/frequency (PUF) scores were evaluated. Bladder capacity was assessed by cystoscopy. Bladder mucosa was collected for Western blot, qRT-PCR, and immunofluorescence staining to compare the expression of VEGI and HIF-1α before and after treatment.

Results: Compared with before treatment, patients showed significant improvements in 24-h voiding frequency (15.32 ± 5.38 times), nocturia (3.71 ± 1.80 times), O'leary-Sant score (20.45 ± 5.62 points), VAS score (41.76 ± 17.88 points), QoL score (3.03 ± 1.44 points), and PUF score (19.95 ± 6.46 points) after treatment (p < 0.05). There was no significant difference in bladder capacity before and after treatment (p ≥ 0.05). The expression levels of VEGI and HIF-1α protein and mRNA were significantly decreased 6 months after treatment compared with before treatment. Immunofluorescence staining results showed that the double positive expression of VEGI and HIF-1α protein in bladder tissue of IC/BPS patients after HBO treatment quantitatively decreased significantly.

Conclusion: This study identified a possible mechanism by which VEGI and HIF-1α expression decreased after HBO treatment due to hypoxia reversal, which improved symptoms in IC/BPS patients.

Keywords: Interstitial cystitis/bladder pain syndrome; hyperbaric oxygen; hypoxia-inducible factor-1α; vascular endothelial growth inhibitor.

Figure 1

Comparisons of average 24-h frequency (A), nocturia (B), O’leary-Sant score (C), VAS score (D), PUF score (E), QoL score (F), and bladder capacity (G) before and after HBO treatment. * a significant difference (p < 0.05). VAS, visual analog scale; PUF, pelvic pain and urgency/frequency; QoL, quality of life;

Figure 2

Typical pictures of the expression of VEGI and HIF-1α protein (A and B) and mRNA (C and D) in IC/BPS patients before and after HBO treatment. * a significant difference (p < 0.05).

Figure 3

Typical pictures of the expression of VEGI and HIF-1α in bladder wall of IC/BPS patients before and after HBO treatment. * a significant difference (p < 0.05).