Gao Wansheng, He Xiangfei, Li Yunlong, Wen Jianguo
Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
Oncotarget. 2017 Oct 10;8(55):94345-94357. doi: 10.18632/oncotarget.21718. eCollection 2017 Nov 7.
Immunophilin ligands are neuroregenerative agents binding to FK506 binding proteins, by which stimulate recovery of neurons in a variety of injury nerves. FK1706 is a novel immunophilin ligand which has neuroprotective and neuroregenerative effects but without immunosuppressive activity. At present, most reports about FK1706 in ameliorating nerve injury and functional recovery are limited to cavernous nerve injury and erectile function recovery. This study aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rat models.
The numbers of regenerated myelinated axons of the pelvic parasympathetic nerve (PPN) in the three groups' rats (FK1706 + ETS, ETS and control groups) were evaluated. Their intravesical pressure (IVP), S100β and growth associated protein 43 (GAP43) expressions were also compared.
In FK1706 + ETS group, 90% the rats showed that the frequency of FG labeled neurons was larger than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB double-labeled neurons was larger than the 5.5 cutoff value. The average maximum of IVP in FK1706 + ETS group reached 76.3% of the value in control group. Their average number of myelinated axons of regenerated PPN reached 80% of the amount in control group. The nerve regeneration-associated markers data indicated that the expression level of S100β and GAP43 in FK1706 + ETS group was approximately 2-fold higher than that of ETS group (P < 0.05).
After end-to-side neurorrhaphy, FK1706 effectively enhanced the nerve regeneration and bladder function recovery.
免疫亲和素配体是与FK506结合蛋白结合的神经再生剂,可刺激多种损伤神经中的神经元恢复。FK1706是一种新型免疫亲和素配体,具有神经保护和神经再生作用,但无免疫抑制活性。目前,关于FK1706改善神经损伤和功能恢复的大多数报道仅限于海绵体神经损伤和勃起功能恢复。本研究旨在证明FK1706对大鼠端侧神经吻合术后神经再生和膀胱功能恢复的影响。
评估三组大鼠(FK1706 + 端侧神经吻合术组、端侧神经吻合术组和对照组)盆腔副交感神经(PPN)再生有髓轴突的数量。还比较了它们的膀胱内压(IVP)、S100β和生长相关蛋白43(GAP43)的表达。
在FK1706 + 端侧神经吻合术组中,90%的大鼠显示FG标记神经元的频率大于3.5的临界值,100%的大鼠显示FG-FB双标记神经元的频率大于5.5的临界值。FK1706 + 端侧神经吻合术组的IVP平均最大值达到对照组值的76.3%。其再生PPN的有髓轴突平均数量达到对照组数量的80%。神经再生相关标志物数据表明,FK1706 + 端侧神经吻合术组中S100β和GAP43的表达水平比端侧神经吻合术组高约2倍(P < 0.05)。
端侧神经吻合术后,FK1706有效地促进了神经再生和膀胱功能恢复。