Chuang Yao-Chi, Huang Chao-Cheng, Kang Hong-Yo, Chiang Po-Hui, Demiguel Fernando, Yoshimura Naoki, Chancellor Michael B
Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China.
J Urol. 2006 Mar;175(3 Pt 1):1158-63. doi: 10.1016/S0022-5347(05)00318-6.
Intraprostatic injection of BTX-A has demonstrated clinical improvement in men with bladder outlet obstruction. We investigated the mechanisms of action of BTX-A on the prostate.
Adult male Sprague-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 alpha(1A) adrenergic receptor and androgen receptor were evaluated by Western blotting.
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 alpha(1A) adrenergic receptor (13%, 80% and 81%) for 5, 10 and 20 U, respectively. There was no significant change in androgen receptors. The effects were decreased 2 weeks after BTX-A treatment.
BTX-A injection into the prostate alters cellular dynamics by inducing apoptosis, inhibiting proliferation and down-regulating alpha(1A) adrenergic receptors. BTX-A may potentially be the drug that has dual actions on the static and dynamic components of benign prostatic hyperplasia.
前列腺内注射肉毒杆菌毒素A（BTX-A）已证实可使膀胱出口梗阻男性患者的临床症状得到改善。我们研究了BTX-A对前列腺的作用机制。
将不同剂量的BTX-A注射到成年雄性Sprague-Dawley大鼠的前列腺内，1或2周后取出前列腺。分别采用苏木精-伊红染色、增殖细胞核抗原染色和TUNEL染色来确定BTX-A对前列腺组织学、增殖指数和凋亡指数的影响。通过蛋白质印迹法评估α（1A）肾上腺素能受体和雄激素受体的变化。
注射BTX-A一周后观察到前列腺普遍萎缩。对于5、10和20单位的剂量，凋亡细胞分别显著增加（12倍、16倍和22倍），增殖细胞分别减少（38%、77%和80%），α（1A）肾上腺素能受体分别减少（13%、80%和81%）。雄激素受体无显著变化。BTX-A治疗2周后效果减弱。
向前列腺内注射BTX-A可通过诱导凋亡、抑制增殖和下调α（1A）肾上腺素能受体来改变细胞动力学。BTX-A可能是一种对良性前列腺增生的静态和动态成分均有双重作用的药物。
