Intraprostatic Reflux of Urine Induces Inflammation in a Rat.

Abstract

We examined whether urine reflux into the prostate can induce prostatic inflammation in a rat and evaluated the effect of α1-adrenoreceptor antagonist. Experiment 1: Male Sprague-Dawley rats were injected with 500 µl of Evans Blue through the urethral orifice. Intravesical pressure was measured, and the prostate was excised to evaluate urine reflux. Experiment 2: Rats were injected with 500 µl urine or saline (control) from the urethral orifice. Silodosin (200 µg/kg/day) was administered to the silodosin group. We evaluated histopathology, the expression of proinflammatory cytokines and oxidative stress markers of the prostate on day 7, after assessing the prostatic microcirculation and cystometrogram. Experiment 1: The histopathology showed that Evans Blue instilled through the urethral orifice entered the prostatic ducts. Intravesical pressure during Evans Blue instillation was 47.7 ± 1.6 cmH2 O (mean ± standard error). Experiment 2: On day 7 after urine instillation through the urethral orifice, histopathology showed infiltrated inflammatory cells in the peri-glandular stroma. Inflammation-associated proteins (IL-1α, IL-1β, IL-6, and TNFα) were upregulated in the urine-instilled rats but not in the silodosin group. Erythrocyte speed on the prostatic surface, immunostaining for hypoxyprobe, and quantification of oxidative stress markers (MDA and HIF-1α) demonstrated prostatic hypoxia in the urine-instilled rats, which was ameliorated in the silodosin group. Cystometrogram revealed a shorter intercontraction interval in the urine-instilled rats, which was prolonged in the silodosin group. Urine reflux into the prostatic duct induces abacterial prostatitis. Silodosin relieved prostatic inflammation and bladder overactivity by increasing microcirculation in the prostate. Prostate 77:164-172, 2017. © 2016 Wiley Periodicals, Inc.