Majima Tsuyoshi, Yamamoto Tokunori, Funahashi Yasuhito, Takai Shun, Matsukawa Yoshihisa, Yoshida Masaki, Gotoh Momokazu
Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Urology, National Center for Geriatrics and Gerontology, Ohbu, Japan.
Low Urin Tract Symptoms. 2017 May;9(2):111-116. doi: 10.1111/luts.12119. Epub 2015 Nov 6.
To evaluate the effect of naftopidil on bladder capillary blood flow using bladder outlet obstruction model rats.
Female Sprague-Dawley rats were divided into three groups: control group, bladder-outlet-obstruction group, and bladder-outlet-obstruction + naftopidil group. Bladder-outlet-obstruction surgery was performed in the bladder-outlet-obstruction and bladder-outlet-obstruction + naftopidil groups. The control group received sham-operation. The bladder-outlet-obstruction + naftopidil group were treated with naftopidil (30 mg/kg) for 14 days after bladder-outlet-obstruction operation, while the control and bladder-outlet-obstruction groups were treated with vehicle. Continuous cystometry was performed 14 days after the surgery. Bladder blood flow was measured after 14 days using a pencil lens charge-coupled device microscopy system. The bladder was then harvested for histology and measuring 8-hydroxy-2'-deoxyguanosine tissue level by enzyme-linked immunosorbent assay.
In cystometry, the bladder-outlet-obstruction rats showed bladder overactivity, while naftopidil treatment improved the cystometric pattern. The blood flow through the submucosal capillaries of the bladder base in the bladder-outlet-obstruction group was lesser than that in the control, whereas the bladder-outlet-obstruction + naftopidil group showed significantly greater blood flow than the bladder-outlet-obstruction group. The bladder tissue in the bladder-outlet-obstruction group showed a tendency to contain more hypertrophic detrusor muscle and inflammatory cells compared to those in the control group, while naftopidil treatment suppressed these histological changes. The 8-hydroxy-2'-deoxyguanosine levels in the bladder tissue significantly differed among the three groups (the bladder-outlet-obstruction group > the bladder-outlet-obstruction + naftopidil group > the control group).
Naftopidil improved bladder overactivity as well as the impaired bladder blood flow.caused by bladder-outlet-obstruction.
利用膀胱出口梗阻模型大鼠评估萘哌地尔对膀胱毛细血管血流的影响。
将雌性斯普拉格-道利大鼠分为三组：对照组、膀胱出口梗阻组和膀胱出口梗阻+萘哌地尔组。对膀胱出口梗阻组和膀胱出口梗阻+萘哌地尔组进行膀胱出口梗阻手术。对照组接受假手术。膀胱出口梗阻+萘哌地尔组在膀胱出口梗阻手术后用萘哌地尔（30mg/kg）治疗14天，而对照组和膀胱出口梗阻组用赋形剂治疗。术后14天进行连续膀胱测压。术后14天使用铅笔透镜电荷耦合器件显微镜系统测量膀胱血流。然后摘取膀胱进行组织学检查，并通过酶联免疫吸附测定法测量8-羟基-2'-脱氧鸟苷组织水平。
在膀胱测压中，膀胱出口梗阻大鼠表现出膀胱活动亢进，而萘哌地尔治疗改善了膀胱测压模式。膀胱出口梗阻组膀胱底部黏膜下毛细血管的血流量低于对照组，而膀胱出口梗阻+萘哌地尔组的血流量明显高于膀胱出口梗阻组。与对照组相比，膀胱出口梗阻组的膀胱组织显示出含有更多肥厚逼尿肌和炎性细胞的趋势，而萘哌地尔治疗抑制了这些组织学变化。三组膀胱组织中的8-羟基-2'-脱氧鸟苷水平存在显著差异（膀胱出口梗阻组>膀胱出口梗阻+萘哌地尔组>对照组）。
萘哌地尔改善了膀胱出口梗阻引起的膀胱活动亢进以及受损的膀胱血流。
