Neuroimmunophilin ligands protect cavernous nerves after crush injury in the rat: new experimental paradigms.
Neuroimmunophilin ligands protect cavernous nerves after crush injury in the rat: new experimental paradigms.
复制标题
神经亲免素配体在大鼠挤压损伤后保护海绵体神经：新的实验范例。
DOI：
10.1016/j.eururo.2006.11.026
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发表时间：
2007
期刊：
影响因子：
23.4
通讯作者：
Steiner,JosephP
中科院分区：
文献类型：
--
作者：
Valentine,Heather;Chen,Yi;Guo,Hongzhi;McCormick,Jocelyn;Wu,Yong;Sezen,SenaF;Hoke,Ahmet;Burnett,ArthurL;Steiner,JosephP
目的：研究口服非免疫抑制性亲免素配体GPI 1046（GPI）对单侧或双侧挤压伤后勃起功能和海绵体神经（CN）组织学的影响方法成年雄性SD大鼠分别腹腔注射GPI 15 mg/kg或经口灌胃30 mg/kg，腹腔注射FK 506 1 mg/kg，或赋形剂对照，用于每种给药途径，就在UCI或BCI之前和损伤后每天最多7天。在治疗的第1天或第7天，测量CN电刺激诱导的勃起功能，并对损伤的CN进行电子显微镜分析。与载体治疗的动物相比，以类似于原型亲免素配体FK 506的方式，向CN损伤的大鼠腹膜内施用GPI保护勃起功能（分别为93%±9%对70%±5%对45%± 1%，p<0.01）。GPI的口服给药引起相同水平的CN损伤的显着保护。GPI 30 mg/kg/d po，每日1次或每日4次，7.5mg/kg，几乎完全保护勃起功能。在更严重的BCI模型中，GPI在CN损伤后24小时口服给药维持勃起功能。损伤的CN的超微结构分析表明，GPI在CN损伤的时间管理，防止约83%的无髓轴突在7天CN injury.CONCLUSIONSThe口服给药的亲免素配体GPI neuroprotects CN和维持勃起功能在大鼠CN挤压伤的各种条件下。
OBJECTIVESWe investigated the effects of the orally bioavailable non-immunosuppressive immunophilin ligand GPI 1046 (GPI) on erectile function and cavernous nerve (CN) histology following unilateral or bilateral crush injury (UCI, BCI, respectively) of the CNs.METHODSAdult male Sprague-Dawley rats were administered GPI 15mg/kg intraperitoneally (ip) or 30mg/kg orally (po), FK506 1mg/kg, ip, or vehicle controls for each route of administration just prior to UCI or BCI and daily up to 7 d following injury. At day 1 or 7 of treatment, erectile function induced by CN electrical stimulation was measured, and electron microscopic analysis of the injured CN was performed.RESULTSIntraperitoneal administration of GPI to rats with injured CN protected erectile function, in a fashion similar to the prototypic immunophilin ligand FK506, compared with vehicle-treated animals (93%±9% vs. 70%±5% vs. 45%±1%, p<0.01, respectively). Oral administration of GPI elicited the same level of significant protection from CN injury. GPI administered po at 30mg/kg/d, dosing either once daily or four times daily with 7.5mg/kg, provided nearly complete protection of erectile function. In a more severe BCI model, po administration of GPI maintained erectile function at 24h after CN injury. Ultrastructural analysis of injured CNs indicated that GPI administered at the time of CN injury prevents degeneration of about 83% of the unmyelinated axons at 7 d after CN injury.CONCLUSIONSThe orally administered immunophilin ligand GPI neuroprotects CNs and maintains erectile function in rats under various conditions of CN crush injury.