Immunophilin ligands promote penile neurogenesis and erection recovery after cavernous nerve injury
Immunophilin ligands promote penile neurogenesis and erection recovery after cavernous nerve injury
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DOI：
10.1097/01.ju.0000089775.88825.ec
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发表时间：
2004-01-01
影响因子：
6.6
通讯作者：
Becker, RE
中科院分区：
文献类型：
--
作者：
Burnett, AL;Becker, RE
目的：我们使用单侧和双侧海绵体神经（CN）损伤的大鼠模型研究了亲免素配体对勃起生理学和海绵体组织学的长期影响。材料和方法：向成年雄性Sprague-Dawley大鼠施用亲免素配体FK 506（5 mg/kg，每日皮下注射5天），非免疫抑制剂FK 506衍生物GPI 1046（3至3-吡啶基）-1-丙基（2秒）-1-（3，3-二甲基-1，2-二氧戊基）-2-吡咯烷羧酸酯）（每天皮下注射40 mg/kg，持续5或28天）或生理盐水，即单侧CN局灶性横断，以及单侧CN局灶性横断和切除对侧CN的5 mm节段（BIL治疗）的组合。在CN损伤后28天，对横断CN进行电刺激和阴茎勃起监测。取出整个阴茎，并对一氧化氮发生器神经元一氧化氮合酶、神经元标记物突触素、内皮标记物CD 31和平滑肌标记物α-肌动蛋白进行化学评价。在单侧治疗组中，FK 506治疗组的勃起恢复明显高于盐水治疗组（（83.5% +/- 9.2% vs 24.3% +/-8.1%，p
Purpose: We investigated the long-term effect of immunophilin ligands on erection physiology and cavernous tissue histology using rat models of unilateral and bilateral cavernous nerve (CN) injury.Materials and Methods: Adult male Sprague-Dawley rats were administered the immunophilin ligand FK506 (5 mg/kg subcutaneously daily for 5 days), the nonimmunosuppressant FK506 derivative GPI1046 (3 to 3-pyridyl)-1-propyl(2 seconds)-1-(3,3-dimethyl- 1,2-dioxopentyl)-2-pyrrolidine carboxylate) (40 mg/kg subcutaneously daily for 5 or 28 days) or saline immediately upon induction of 2 paradigms of cavernous nerve injury, namely focal transection of the CN unilaterally, and a combination of focal transection of the CN unilaterally and excision of a 5 mm segment of contralateral CN (BIL treated). At 28 days following CN injury electrical stimulation of the transected CN and penile erection monitoring were performed. Whole penes were removed and evaluated immunohistochemically for the nitric oxide generator neuronal nitric oxide synthase, the neuronal marker synaptophysin, the endothelial marker CD31 and the smooth muscle marker alpha-actin.Results: In unilaterally treated groups erection recovery was significantly greater in FK506 treated than in saline treated animals ((83.5% +/- 9.2% vs 24.3% +/- 8.1%, p