FK1706 enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat
FK1706 enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat
复制标题
DOI：
10.1111/j.1743-6109.2007.00438.x
复制
发表时间：
2007-03-01
影响因子：
3.5
通讯作者：
Lue, Tom F.
中科院分区：
文献类型：
--
作者：
Bella, Anthony J.;Hayashi, Narihiko;Lue, Tom F.
介绍。神经生物学的进步引起了临床对开发保护性和再生性神经调节策略的兴趣激增，因为前列腺癌的手术治疗通常会导致神经元损伤和性功能丧失。探讨非免疫抑制剂亲免素配体 FK1706 对大鼠双侧海绵神经挤压损伤后勃起功能恢复的剂量依赖性功效。主要结果指标。通过海绵神经电刺激评估勃起功能的恢复，并报告为海绵内压（ICP）和曲线下面积（AUC）的最大增加。比较各组之间动物体重的变化、治疗过程的完成百分比和存活率。方法。将 35 只 Sprague-Dawley 雄性大鼠随机分为 5 个相等组：7 只动物接受假手术，而 28 只动物接受双侧海绵体神经挤压损伤，然后单独皮下注射载体（1.0 mL/kg），或低剂量（0.1 mg/kg）、中剂量（0.32 mg/kg）或高剂量（1.0 mg/kg）FK1706，每周 5 天，持续 8 周。 结果。假手术组没有出现勃起功能障碍（平均最大 ICP 增加 100.8 +/- 6.3 cmH(2)O），而神经损伤和载体治疗使 ICP 反应显着降低至 34.4 +/- 12.8 cmH(2)O。高剂量 FK106 治疗的平均 ICP 增加为 73.9 +/- 6.3 cmH(2)O（与媒介物相比，P < 0.01），而低剂量和中剂量治疗的平均 ICP 增加为 58.3 +/- 7.4 cmH(2)O 和 56.9 +/- 8.3 (P > 0.05)。使用 AUC 数据观察到类似的逐步发现。各组之间没有出现显着的最大主动脉血压或体重差异，并且所有动物都完成了治疗。结论。高剂量皮下注射 FK1706 治疗可促进大鼠双侧海绵神经挤压损伤后勃起功能的恢复。没有观察到组间体重变化存在显着差异，所有动物都完成了 8 周的治疗过程。
Introduction. Advances in neurobiology have led to a surge of clinical interest in the development of protective and regenerative neuromodulatory strategies, as surgical therapies for prostate cancer often result in neuronal damage and debilitating loss of sexual function.Aim. To investigate the dose-dependent efficacy of FK1706, a nonimmunosuppressant immunophilin ligand, for the recovery of erectile function following bilateral cavernous nerve crush injury in the rat.Main Outcome Measures. Recovery of erectile function was assessed by cavernous nerve electrostimulation and reported as maximal increase of intracavernous pressure (ICP) and area under the curve (AUC). Changes in animal weights, percentage completion of treatment course, and survival were compared between groups.Methods. Thirty-five Sprague-Dawley male rats were randomly divided into five equal groups: seven animals received a sham operation, whereas 28 animals underwent bilateral cavernous nerve crush injury, followed by subcutaneous injection of vehicle alone (1.0 mL/kg), or low (0.1 mg/kg), medium (0.32 mg/kg), or high dose (1.0 mg/kg) FK1706 5 days per week for 8 weeks.Results. Erectile dysfunction did not occur in the sham group (mean maximal ICP increase of 100.8 +/- 6.3 cmH(2)O), whereas nerve injury and vehicle treatment produced a significant reduction in ICP response to 34.4 +/- 12.8 cmH(2)O. The mean ICP increase for high-dose FK106 treatment was 73.9 +/- 6.3 cmH(2)O (P < 0.01 vs. vehicle) compared with 58.3 +/- 7.4 cmH(2)O and 56.9 +/- 8.3 for low and medium doses (P > 0.05). Similar stepwise findings were observed using AUC data. No significant maximal aortic blood pressure or weight differences occurred between groups and all animals completed treatment.Conclusion. High-dose subcutaneous FK1706 therapy promoted recovery of erectile function following bilateral cavernous nerve crush injury in the rat. No significant differences between groups were observed for changes in weight, and the 8-week treatment course was completed for all animals.