Therapeutic effect of TAC-302, a cyclohexenoic fatty alcohol derivative, on bladder denervation-related storage and voiding dysfunctions in rats
Therapeutic effect of TAC-302, a cyclohexenoic fatty alcohol derivative, on bladder denervation-related storage and voiding dysfunctions in rats
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DOI：
10.1002/nau.23571
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发表时间：
2018-09-01
影响因子：
2
通讯作者：
Sasaki, Eiji
中科院分区：
文献类型：
--
作者：
Yoshida, Shohei;Noma, Takahisa;Sasaki, Eiji
目的探讨环己烯酸脂肪醇衍生物TAC-302对膀胱出口梗阻（BOO）大鼠膀胱去神经相关的储存和排尿功能障碍的治疗作用。两周后，将BOO大鼠分为两组，分别口服溶剂或10 mg/kg TAC-302，每天两次，持续4周。对膀胱肌层进行尿动力学和免疫组织化学评价。在另一项研究中，BOO大鼠在膀胱测压时静脉注射坦索罗辛。逼尿肌收缩力在每组进行了评估，使用修改后的Shafer的nomogl.ResultsTwo周后BOO，大鼠表现出显着增加非排尿收缩（NVCs）和残余尿量（RUV）相比，假手术组。此外，与假手术组相比，BOO后6周，BOO载体大鼠显示NVCs和RUV显著增加，逼尿肌收缩力和膀胱中的神经纤维密度降低。口服TAC-302可部分改善BOO诱导的膀胱去神经支配。口服TAC-302可显著降低NVCs的振幅和频率（P
AimsTo evaluate the therapeutic effect of TAC-302, a cyclohexenoic fatty alcohol derivative, on bladder denervation-related storage and voiding dysfunctions in rats with bladder outlet obstruction (BOO).MethodsBOO was achieved by partial ligature of the proximal urethra in female rats. Two weeks later, BOO rats were divided into two groups and treated orally with vehicle or 10mg/kg TAC-302 twice a day for 4 weeks. Urodynamic and immunohistochemical evaluation of the bladder muscle layer was performed. In another study, the BOO rats were treated with intravenous tamsulosin at cystometry. The detrusor contractility in each group was evaluated using the modified Shafer's nomogram.ResultsTwo weeks after BOO, the rats showed significant increases in non-voiding contraction (NVCs) and residual urine volume (RUV) compared to the sham group. Moreover, 6 weeks after BOO, BOO vehicle rats showed significant increases in NVCs and RUV and decreases in detrusor contractility and in the nerve fiber density in the urinary bladder compared to the sham group. BOO-induced denervation of the urinary bladder was partially improved by oral treatment with TAC-302. Oral treatment with TAC-302 significantly reduced the amplitude and frequency of NVCs (P