Nishiyama Yasuhiro, Yokoyama Teruhiko, Tomizawa Kazuhito, Okamura Kikuo, Yamamoto Yumiko, Matsui Hideki, Oguma Keiji, Nagai Atsushi, Kumon Hiromi
Department of Urology, Okayama University Graduate School of Medicine and Dentistry, Japan.
Urology. 2009 Aug;74(2):436-9. doi: 10.1016/j.urology.2009.01.047. Epub 2009 Apr 15.
To investigate the efficacy of a newly purified neurotoxin (NTX) in male rat prostates. Several reports have suggested that intraprostatic injection of botulinum toxin type A has demonstrated efficacy against symptomatic benign prostatic hyperplasia. NTXs associate with nontoxic components and form large complexes designated "progenitor toxins." In general, progenitor toxins are used, because they are easily obtained and are more stable than NTXs. However, they have side effects for some patients in whom anti-progenitor toxins, including anti-NTX antibodies, are produced after several injections. We purified NTXs without their nontoxic components using a simple procedure.
Adult male Sprague-Dawley rats were injected with 5 U of NTX or saline into their prostates, which were harvested and weighed after 1 or 4 weeks. The effects of the NTX on the prostate were histologically and immunohistochemically studied using hematoxylin-eosin, synaptophysin, and terminal deoxynucleotidyl-mediated deoxyuridine triphosphate nick end labeling staining.
In the NTX-treated rats, the prostate weight was reduced and atrophy and diffuse apoptosis were observed. Moreover, synaptophysin-positive cells in the epithelium were decreased after NTX injection.
Intraprostatic NTX injection induces prostate apoptosis and atrophic change in the rat prostate. These results suggest that NTX injection might be a promising material for treatment of patients with benign prostatic hyperplasia.
研究一种新纯化的神经毒素(NTX)对雄性大鼠前列腺的疗效。有几份报告表明,前列腺内注射A型肉毒杆菌毒素已显示出对有症状的良性前列腺增生有效。NTX与无毒成分结合形成称为“祖毒素”的大复合物。一般使用祖毒素,因为它们易于获得且比NTX更稳定。然而,对于一些患者,多次注射后会产生包括抗NTX抗体在内的抗祖毒素,从而产生副作用。我们采用简单的方法纯化了不含无毒成分的NTX。
将5 U的NTX或生理盐水注射到成年雄性Sprague-Dawley大鼠的前列腺中,1周或4周后取出前列腺并称重。使用苏木精-伊红、突触素和末端脱氧核苷酸介导的脱氧尿苷三磷酸缺口末端标记染色,对NTX对前列腺的影响进行组织学和免疫组织化学研究。
在接受NTX治疗的大鼠中,前列腺重量减轻,观察到萎缩和弥漫性凋亡。此外,注射NTX后上皮中突触素阳性细胞减少。
前列腺内注射NTX可诱导大鼠前列腺细胞凋亡和萎缩性改变。这些结果表明,注射NTX可能是治疗良性前列腺增生患者的一种有前景的材料。