TAC-302 promotes neurite outgrowth of isolated peripheral neurons and prevents bladder denervation related bladder dysfunctions following bladder outlet obstruction in rats
TAC-302 promotes neurite outgrowth of isolated peripheral neurons and prevents bladder denervation related bladder dysfunctions following bladder outlet obstruction in rats
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DOI：
10.1002/nau.23375
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发表时间：
2018-02-01
影响因子：
2
通讯作者：
Sasaki, Eiji
中科院分区：
文献类型：
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作者：
Yoshida, Shohei;Orimoto, Naoki;Sasaki, Eiji
目的观察环己烯类脂肪醇衍生物TAC-302促进培养的大鼠背根神经节(DRG)神经元突起生长的作用，以及TAC-302对膀胱出口梗阻(BOO)大鼠膀胱失神经相关储存和排尿功能障碍的保护作用。培养24小时后，对细胞数量和突起长度进行量化。通过部分结扎雌性大鼠近端尿路形成BOO模型。将BOO大鼠分为3组，分别给予TAC-302 3 mg/kg和30 mg/kg，每日2次灌胃，连续4周。在清醒状态下进行膀胱测压。结果TAC-302显著促进培养的背根节神经元突起生长，并呈剂量依赖关系。与假手术大鼠相比，BOO大鼠的膀胱神经支配面积减少。口服TAC-302可部分预防BOO所致的膀胱失神经。TAC-302组无排尿收缩频率(NVC)和残余尿量(RUV)明显低于BOO组(P
AimsTo evaluate the ability of TAC-302, a cyclohexenoic fatty alcohol derivative, to enhance neurite outgrowth in cultured rat dorsal root ganglion (DRG) neurons, and the preventive effects of TAC-302 on bladder denervation-related storage and voiding dysfunctions in rats with bladder outlet obstruction (BOO).MethodsRat DRG neurons were cultured in the presence of TAC-302. Cell numbers and neurite lengths were quantified after a 24h culture. BOO was achieved by partial ligature of the proximal urethra in female rats. BOO rats were divided into three groups and orally treated with vehicle of 3 or 30mg/kg TAC-302 twice a day for 4 weeks. Cystometry was performed under conscious conditions. Immunohistochemical staining using anti-PGP9.5 of the bladder muscle layer was performed, and the innervation area was scored.ResultsTAC-302 significantly and dose-dependently increased neurite outgrowth in cultured DRG neurons. BOO rats showed a decreased innervation area in the urinary bladder compared to sham-operated rats. BOO-induced denervation of the urinary bladder was partially prevented by oral treatment with TAC-302. TAC-302 significantly reduced the frequency of non-voiding contraction (NVC) and residual urine volume (RUV) compared with the BOO vehicle group (P