| Summary: | 碩士 === 國立中山大學 === 生物科學系研究所 === 95 === Intraprostatic injection of BTX-A has demonstrated clinical improvement in men with bladder out let obstruction. Firstly, we investigated the mechanisms of action of BTX-A on the prostate. Secondly, an animal model for nonbacterial prostatitis in rats was developed using intraprostatic injection of capsaicin, an agent thought to excite c-afferent fibers and cause neurogenic inflammation. The analgesic and anti-inflammatory properties of Botulinum toxin type A (BoNT-A) was tested in this model. (1) Adult male Spragu-Dawley rats were injected with varying doses of BTX-A into the prostate, and the prostates were harvested after 1 or 2 weeks. The effects of BTX-A on prostate histology, and the proliferative and apoptotic indexes were determined using hematoxylin and eosin staining, proliferative cell nuclear antigen staining and TUNEL staining, respectively. Changes in a1A adrenergic receptor and androgen receptor were evaluated by Western blotting.
(2) Adult male Spragu-Dawley rats were injected with varying doses of capsaicin into
the prostate. The nociceptive effects of capsaicin were evaluated for 30 min by using a behavior approach; the prostate was removed for histology and cyclooxygenase (COX) 2 concentration measurement. Evans blue (50mg/kg) was also injected intravenously to assess for plasma protein extravasation. The other set of animals were injected with up to 20U of BoNT-A into the prostates 1 wk prior to intraprostatic injection of 1000umol/l capsaicin. (1) One week after BTX-A injection generalized prostate atrophy was observed. There was a significant increase in apoptotic cells (12, 16 and 22-fold), and decrease in proliferative cells (38%, 77% and 80%) and a1A adrenergic receptor (13%, 80% and 81%) for 5U, 10U and 20U, respectively. There was no significant change in androgen receptors. The effects were decreased 2 weeks after BTX-A treatment. (2) Capsaicin dose dependently induced modifications in pain behavior closing of the eyes, hypolocomotion, and inflammatory changes: increase of inflammatory cell accumulation, COX2 expression, and plasma extravasation at the acute stage, but completely recovered at 1 wk. BoNT-A pretreatment dose dependently reversed pain behavior and inflammation. BoNT-A 20U significantly decreased inflammatory cell accumulation, COX2 expression, and Evans blue extraction (82.1%, 93.0% and 50.4, respectively), and reduced pain behavior (66.% for eye score and 46.5% for locomotion score). Conclusion (1): BTX-A injection into the prostate alters cellular dynamics by inducing apoptosis, inhibiting proliferation and down-regulating a1A adrenergic receptors. BTX-A may potentially be the drug that has dual actions on the static and dynamic components of benign prostatic hyperplasia. (2): Intraprostatic capsaicin injection induced neurogenic prostatitis and prostatic pain, and may be a useful research model. BoNT-A produced anti-inflammatory and analgesic effects, and support clinical evaluation in prostatitis.
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