Department of Urology, Hospital S. João, Porto, Portugal.
Eur Urol. 2009 Jul;56(1):134-40. doi: 10.1016/j.eururo.2008.07.003. Epub 2008 Jul 15.
Previous studies in humans, dogs, and rats have shown that intraprostatic injection of botulinum neurotoxin type A (BoNTA) reduces gland size.
To investigate the role of eventual impairment of sympathetic, parasympathetic, and sensory nerves to gland atrophy after intraprostatic BoNTA administration.
DESIGN, SETTING, AND PARTICIPANTS: Adult male Wistar rats weighing 300-350 g were used.
Animals were injected in the prostate ventral lobes with 0.2 ml of saline (n=6) or the same volume containing 10 U BoNTA (BOTOX) (n=18). Six rats treated with BoNTA further received the adrenergic agent phenylephrine (PHE, 0.05 mg/kg per day), six received the cholinergic drug bethanechol (2 mg/kg per day), and six received subcutaneous saline. Animals were sacrificed 1 wk later.
Prostates were weighed, fixed, and stained for sympathetic (tyrosine hydroxylase [TH]), parasympathetic (vesicular acetylcholine [ACh] transporter [VAChT]), and sensory nerve (calcitonin gene-related peptide [CGRP]) visualisation. Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labelling (TUNEL) reaction was performed to investigate apoptosis.
Prostate weight in controls was 1.82+/-0.24 mg/100 g of rat weight. In BoNTA-treated rats, weight decreased to 1.28+/-0.18 mg /100 g of rat weight (p=0.002). In BoNTA plus PHE-treated rats, prostate weight was similar to controls: 1.78+/-0.27 (p=0.87). In rats treated with BoNTA plus bethanechol, weight was less than controls: 1.41+/-0.17 (p=0.01). The number of TH-positive fibres was markedly reduced after BoNTA (p<0.001). VAChT- and CGRP-positive fibres were scarce in controls, preventing further evaluation. Rats treated with BoNTA had more TUNEL-positive cells than controls (p<0.001) and rats treated with BoNTA plus PHE (p<0.001). There were no differences between the BoNTA and BoNTA plus bethanechol groups (p=0.81). Although showing atrophy after BoNTA injection, rat prostates do not develop benign prostatic hyperplasia (BPH). Thus, present findings should be used cautiously to explain prostate atrophy seen in men with BPH treated with BoNTA.
Prostate atrophy induced by BoNTA in the rat may be the result of sympathetic nerve impairment and decreased adrenergic stimulation of the gland. Data indirectly suggest that sympathetic drive plays a role in prostate-size regulation.
先前在人类、狗和大鼠中的研究表明，前列腺内注射肉毒毒素 A（BoNTA）可减少腺体体积。
研究前列腺内 BoNTA 给药后，交感、副交感和感觉神经最终受损对腺体萎缩的作用。
设计、地点和参与者：使用体重为 300-350g 的成年雄性 Wistar 大鼠。
动物被注射到前列腺腹叶中 0.2ml 的生理盐水（n=6）或含有 10U BoNTA（BOTOX）的相同体积（n=18）。用 BoNTA 治疗的 6 只大鼠进一步接受去甲肾上腺素能药物苯肾上腺素（PHE，每天 0.05mg/kg），6 只接受胆碱能药物氨甲酰胆碱（2mg/kg/天），6 只接受皮下生理盐水。1 周后处死动物。
前列腺称重、固定和染色以显示交感神经（酪氨酸羟化酶[TH]）、副交感神经（囊泡乙酰胆碱[VAChT]转运蛋白）和感觉神经（降钙素基因相关肽[CGRP]）。末端脱氧核苷酸转移酶生物素-dUTP 缺口末端标记（TUNEL）反应用于研究细胞凋亡。
对照组前列腺重量为 1.82+/-0.24mg/100g 大鼠体重。BoNTA 治疗组大鼠的前列腺重量降至 1.28+/-0.18mg/100g 大鼠体重（p=0.002）。在 BoNTA 加 PHE 治疗的大鼠中，前列腺重量与对照组相似：1.78+/-0.27（p=0.87）。在接受 BoNTA 加氨甲酰胆碱治疗的大鼠中，体重小于对照组：1.41+/-0.17（p=0.01）。BoNTA 后 TH 阳性纤维数量明显减少（p<0.001）。VAChT 和 CGRP 阳性纤维在对照组中很少，无法进一步评估。BoNTA 治疗的大鼠比对照组有更多的 TUNEL 阳性细胞（p<0.001）和 BoNTA 加 PHE 治疗的大鼠（p<0.001）。BoNTA 组和 BoNTA 加氨甲酰胆碱组之间无差异（p=0.81）。尽管 BoNTA 注射后前列腺出现萎缩，但大鼠前列腺并未发生良性前列腺增生（BPH）。因此，目前的发现应谨慎用于解释接受 BoNTA 治疗的 BPH 男性的前列腺萎缩。
BoNTA 在大鼠中引起的前列腺萎缩可能是交感神经损伤和腺体去甲肾上腺素刺激减少的结果。数据间接表明，交感神经驱动在前列腺大小调节中起作用。
