Apoptosis and Effects of Intracavernous Bone Marrow Cell Injection in a Rat Model of Postprostatectomy Erectile Dysfunction
Apoptosis and Effects of Intracavernous Bone Marrow Cell Injection in a Rat Model of Postprostatectomy Erectile Dysfunction
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DOI：
10.1016/j.eururo.2008.09.059
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发表时间：
2009-10-01
期刊：
影响因子：
23.4
通讯作者：
Yiou, Rene
中科院分区：
文献类型：
--
作者：
Fall, Papa Ahmed;Izikki, Mohamed;Yiou, Rene
目的：探讨双侧海绵体神经消融 (BCNA) 大鼠模型中前列腺切除术后勃起功能障碍 (pPED) 的病理生理学，并评估局部骨髓单核细胞 (BMMNC) 注射对 BCNA 引起的勃起功能障碍 (ED) 和海绵体细胞异常的影响。设计、设置和参与者：这是一项在 BCNA 的 Fisher 大鼠中进行的实验研究。测量：研究了对电刺激盆腔神经节的勃起反应。检查海绵组织以确定正在凋亡的细胞类型，并使用实时定量聚合酶链式反应 (RTQ-PCR) 和蛋白质印迹检测神经元一氧化氮合酶 (nNOS) 和内皮一氧化氮合酶 (eNOS) 的蛋白质和基因表达的变化。研究了局部BMMNC注射对这些参数的影响。结果和局限性：在结缔组织间充质细胞以及血管平滑肌和内皮细胞中观察到弥漫性凋亡。与假手术对照组相比，nNOS 和 eNOS 水平在 3 周后下降，5 周后恢复正常（eNOS）或升高（nNOS），表明自发神经再生。尽管nNOS恢复，但5周后对电刺激的勃起反应仍然受损，此时间充质细胞凋亡是主要的持续性生物学异常。 BMMNC 注射减少了凋亡细胞数量，加速了 nNOS 和 eNOS 的正常化，并在第 5 周部分恢复了勃起反应。结论：大量细胞凋亡可能在 pPED 的病理生理学中发挥关键作用。在该动物模型中，尽管有自发的神经再生，细胞凋亡仍持续存在，这表明 BCNA 诱导的细胞功能障碍的过程与神经支配无关。 BMMNC 通过抑制细胞凋亡来改善勃起功能，并有望修复根治性前列腺切除术 (RP) 引起的阴茎细胞损伤。 (C) 2008 年欧洲泌尿外科协会。由 Elsevier B.V. 出版。保留所有权利。
Objectives: To investigate the pathophysiology of postprostatectomy erectile dysfunction (pPED) in a rat model of bilateral cavernous nerve ablation (BCNA) and to assess the effects of local bone marrow mononuclear cell (BMMNC) injection on erectile dysfunction (ED) and cavernosal cellular abnormalities caused by BCNA.Design, setting, and participants: This was an experimental study in Fisher rats with BCNA.Intervention: Intervention included BNCA, electrical stimulation of the pelvic ganglion, and local BMMNC injection.Measurements: Erectile responses to electric pelvic ganglion stimulation were studied. Cavernous tissue was examined to determine the cell types undergoing apoptosis and to detect changes in Protein and gene expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) using real-time quantitative polymerase chain reaction (RTQ-PCR) and Western blotting. The effects of local BMMNC injection on these parameters were studied.Results and limitations: Diffuse apoptosis was noted in the connective tissue mesenchymal cells and vascular smooth muscle and endothelial cells. Compared with sham-operated controls, nNOS and eNOS levels were decreased after 3 wk and were normal (eNOS) or increased (nNOS) after 5 wk, suggesting spontaneous nerve regeneration. Despite nNOS recovery, erectile responses to electrical stimulation remained impaired after 5 wk, when mesenchymal cell apoptosis was the main persistent biologic abnormality. BMMNC injection decreased apoptotic cell numbers, accelerated the normalisation of nNOS and eNOS, and partially restored erectile responses at week 5.Conclusions: Massive cell apoptosis may play a key role in the pathophysiology of pPED. In this animal model, apoptosis persisted despite spontaneous nerve regeneration, suggesting that the course of BCNA-induced cell dysfunction was independent of reinnervation. BMMNC improved erectile function by inhibiting apoptosis and may hold promise for repairing penile cell damage caused by radical prostatectomy (RP). (C) 2008 European Association Of Urology. Published by Elsevier B.V. All rights reserved.