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大鼠双侧海绵体神经损伤后,通过海绵体内注射内皮祖细胞恢复勃起功能。

Restoration of erectile function with intracavernous injections of endothelial progenitor cells after bilateral cavernous nerve injury in rats.

作者信息

Liao C H, Wu Y N, Lin Y H, Syu Huang R F, Liu S P, Chiang H S

机构信息

Division of Urology, Department of Surgery, Cathay General Hospital, New Taipei City, Taiwan.

School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.

出版信息

Andrology. 2015 Sep;3(5):924-32. doi: 10.1111/andr.12085.

DOI:10.1111/andr.12085
PMID:26311341
Abstract

Endothelial progenitor cells (EPCs) are bone marrow-derived endothelial cells capable of circulating, proliferating, and differentiating into mature endothelial cells. Circulating EPCs can be directly recruited to some extent at sites of injury, and their administration could accelerate repair or endothelialization of the damaged tissue. We investigated the effects of intracavernous injections of EPCs into the corpora cavernosa of rats with erectile dysfunction (ED) caused by bilateral cavernous nerve (CN) injury. Overall, 24 male Sprague-Dawley rats were randomized into three groups: sham surgery, vehicle-only, or EPC treatment. Rats in the EPC treatment and vehicle-only groups were subjected to bilateral CN injury before injection of EPCs or vehicle, respectively, into the corpora cavernosa. Four weeks after surgery, erectile function was assessed by measuring maximum intracavernosal pressure (ICP), change in ICP, area under the ICP curve, and ratio of change in ICP and mean arterial pressure (MAP; ΔICP/MAP). Penile tissue was histomorphometrically analyzed for the expression of neural nitric oxide synthase (nNOS), neurofilament-1 (NF-1), von Willebrand factor (vWF), endothelial NOS (eNOS), and smooth muscle cell content. Maximum ICP and all other functional parameters of erectile function were significantly reduced in the vehicle-only group vs. the sham and EPC treatment groups (all p < 0.001). Smooth muscle cell content was decreased in the vehicle-only vs. the sham and EPC treatment groups (both p < 0.01). Expressions of vWF and eNOS in the dorsal artery were significantly higher in the EPC treatment than the vehicle-only group (p < 0.05). In conclusion, EPC treatment restored erectile function in a rat model of bilateral CN injury through recruitment of EPCs toward the dorsal artery and preservation of smooth muscle cells in the corpus cavernosum. These findings elucidate the therapeutic potential of EPCs for treating ED in humans.

摘要

内皮祖细胞(EPCs)是源自骨髓的内皮细胞,能够循环、增殖并分化为成熟的内皮细胞。循环中的EPCs在一定程度上可直接被募集到损伤部位,给予EPCs可加速受损组织的修复或内皮化。我们研究了向双侧海绵体神经(CN)损伤所致勃起功能障碍(ED)大鼠的海绵体内注射EPCs的效果。总共24只雄性Sprague-Dawley大鼠被随机分为三组:假手术组、单纯注射溶剂组或EPC治疗组。EPC治疗组和单纯注射溶剂组的大鼠分别在向海绵体内注射EPCs或溶剂之前接受双侧CN损伤。术后4周,通过测量海绵体内最大压力(ICP)、ICP变化、ICP曲线下面积以及ICP变化与平均动脉压(MAP;ΔICP/MAP)的比值来评估勃起功能。对阴茎组织进行组织形态计量学分析,以检测神经型一氧化氮合酶(nNOS)、神经丝-1(NF-1)、血管性血友病因子(vWF)、内皮型一氧化氮合酶(eNOS)的表达以及平滑肌细胞含量。与假手术组和EPC治疗组相比,单纯注射溶剂组的最大ICP及勃起功能的所有其他功能参数均显著降低(均p < 0.001)。与假手术组和EPC治疗组相比,单纯注射溶剂组的平滑肌细胞含量减少(均p < 0.01)。EPC治疗组背动脉中vWF和eNOS的表达显著高于单纯注射溶剂组(p < 0.05)。总之,EPC治疗通过使EPCs向背动脉募集并保留海绵体中的平滑肌细胞,恢复了双侧CN损伤大鼠模型的勃起功能。这些发现阐明了EPCs在治疗人类ED方面的治疗潜力。

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