| Summary: | 博士 === 慈濟大學 === 醫學科學研究所 === 99 === Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by bladder pain, frequency and nocturia. Chronic inflammation and impaired urothelial homeostasis are possible pathogenesis of IC/PBS. This study aimed to investigate if bladder inflammation could directly modulate the signaling pathway of increased urothelial cell apoptosis in IC/PBS, and the mechanism of IC/PBS patients recovered after intravesical BoNT-A injection, an antinociceptive effect on bladder afferent pathways in patients with IC/PBS. There was a significant correlation between increased apoptotic cell number and the activated mast cell in IC/PBS bladders. Moreover, decreased expression of E-cadherin showed an abnormal barrier function and was significantly correlated with increased bladder visual analog pain score. Furthermore, protein-antibody array analysis and immunoblotting showed that several inflammatory and apoptotic molecules were increased in the IC/PBS bladder samples, including phospho-p53 (Ser 15), Bad, Bax, cleaved caspase-3, phospho-p38 and TNFα. The in vitro analysis also showed that apoptotic process could be induced by TNFα treatment and anisomycin stimulation in normal urothelial cells. Base on these results, we suggested that tissue damage and abnormal urothelium of bladder might be regulated concurrently by inflammatory signals such as p38 MAPK and TNFα in IC/PBS. These results help to explain the pathogenesis of IC/PBS. Our clinical results suggest that BoNT-A has an antinociceptive effect on bladder afferent pathways in patients with IC/PBS, producing both symptomatic and functional improvements. Besides the mast cell activity was decreased, we also found that several inflammatory and angiogenesis molecules were decreased after BoNT-A injection, but urothelial apoptosis was not inhibited in IC/PBS. This study indicated that inflammatory effect could be reduced due to the bladder intravesical BoNT-A injection and it could provide an evidence for the existing pathophysiology of IC/PBS as well as the actual mechanism of action of BoNT-A in treating IC/PBS.
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