Separate or combined treatments with daily sildenafil, molsidomine, or muscle-derived stem cells prevent erectile dysfunction in a rat model of cavernosal nerve damage.
Separate or combined treatments with daily sildenafil, molsidomine, or muscle-derived stem cells prevent erectile dysfunction in a rat model of cavernosal nerve damage.
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每日使用西地那非、吗多明或肌肉来源的干细胞单独或联合治疗可预防海绵体神经损伤大鼠模型的勃起功能障碍。
DOI：
10.1111/j.1743-6109.2012.02913.x
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Gonzalez-Cadavid NF
中科院分区：
文献类型：
--
作者：
Kovanecz I;Rivera S;Nolazco G;Vernet D;Segura D;Gharib S;Rajfer J;Gonzalez-Cadavid NF
简介在老年和双侧海绵体神经切除 (BCNR) 勃起功能障碍模型中，长期每日给予大鼠 5 型磷酸二酯酶 (PDE5) 抑制剂可预防或逆转体静脉闭塞功能障碍 (CVOD) 以及平滑肌细胞 (CSMC) 损失和纤维化。在衰老大鼠模型中，骨骼肌干细胞 (MDSC) 的体内植入可逆转 CVOD。一氧化氮 (NO) 和环磷酸鸟苷可以调节干细胞谱系。目的在 BCNR 模型中研究较低剂量的西地那非（单独或与 MDSC 或 NO 供体吗多明联合使用）对 CVOD 和潜在的身体组织病理学的影响。主要结果测量大鼠身体组织中的 CVOD、组织学和生化标志物。方法将接受 BCNR 的大鼠维持45天，或者不治疗，或者接受西地那非在水中或舌后注射10、2.5和1.25 mg/kg/天（中、低和极低剂量），或腹膜内莫西多明，或单独或联合将MDSC植入海绵体。海绵体测量法评估了 CVOD。通过 Masson 三色法对阴茎切片进行组织病理学评估，对 α-平滑肌肌动蛋白 (ASMA) 进行免疫组织化学评估，或对神经元一氧化氮合酶 (nNOS)/神经丝 70 进行免疫荧光评估，并通过蛋白质印迹对新鲜组织中的各种标记物和天狼星红进行胶原蛋白评估。结果所有治疗均使勃起功能正常化（下降率），并且大多数治疗都增加了阴茎组织切片中的 CSMC/胶原蛋白比率和 ASMA 表达，并减少阴茎干中的胶原蛋白含量。 MDSC 还增加 nNOS 和脑源性神经营养因子。联合治疗并不优于单独给予MDSC或西地那非，并且上调了PDE5。结论。降低西地那非连续长期给药的剂量仍能维持先前观察到的BCNR大鼠的CVOD预防作用，但对潜在的组织病理学效果较差。与衰老大鼠模型一样，MDSC 也可以抵消 CVOD，但补充极低剂量的西地那非并不能改善结果。
IntroductionLong-term daily administration of phosphodiesterase type 5 (PDE5) inhibitors in the rat prevents or reverses corporal veno-occlusive dysfunction (CVOD) and smooth muscle cell (CSMC) loss and fibrosis, in both aging and bilateral cavernosal nerve resection (BCNR) models for erectile dysfunction. In the aging rat model, corporal implantation of skeletal muscle-derived stem cells (MDSC) reverses CVOD. Nitric oxide (NO) and cyclic guanosine monophosphate can modulate stem cell lineage.AimTo investigate in the BCNR model the effects of sildenafil at lower doses, alone or in combination with MDSC or the NO donor molsidomine, on CVOD and the underlying corporal histopathology.Main Outcomes MeasuresCVOD, histological, and biochemical markers in rat corporal tissue.MethodsRats subjected to BCNR were maintained for 45 days either untreated, or received sildenafil in the water or retrolingually at 10, 2.5, and 1.25 mg/kg/day (medium, low, and very low doses), or intraperitoneal molsidomine, or MDSC implantation into the corpora cavernosa separately or in combination. Cavernosometry evaluated CVOD. Histopathology was assessed on penile sections by Masson trichrome, immunohistochemistry for α-smooth muscle actin (ASMA), or immunofluorescence for neuronal nitric oxide synthase (nNOS)/neurofilament 70, and in fresh tissue by Western blot for various markers and picrosirius red for collagen.ResultsAll treatments normalized erectile function (drop rate), and most increased the CSMC/collagen ratio and ASMA expression in corporal tissue sections, and reduced collagen content in the penile shaft. MDSC also increased nNOS and brain-derived neurotrophic factor. The combination treatment was not superior to MDSC or sildenafil given alone, and upregulated PDE5.Conclusions.Lowering the dose of a continuous long-term sildenafil administration still maintained the prevention of CVOD in the BCNR rat previously observed, but it was less effective on the underlying histopathology. As in the aging rat model, MDSC also counteracted CVOD, but supplementation with very low-dose sildenafil did not improve the outcome.
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DOI：
10.1111/j.1743-6109.2009.01697.x
发表时间：
2010-04
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Huang YC;Ning H;Shindel AW;Fandel TM;Lin G;Harraz AM;Lue TF;Lin CS
通讯作者：
Lin CS
DOI：
10.1007/978-1-60327-029-8_13
发表时间：
2010-01-01
期刊：
FREE RADICALS AND ANTIOXIDANT PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Deng, W.;Bivalacqua, T. J.;Kadowitz, Philip J.
通讯作者：
Kadowitz, Philip J.
影响因子：
7.2
作者：
Ho MH;Heydarkhan S;Vernet D;Kovanecz I;Ferrini MG;Bhatia NN;Gonzalez-Cadavid NF
通讯作者：
Gonzalez-Cadavid NF
影响因子：
2.1
作者：
Ferrini, Monica G.;Davila, Hugo H.;Rajfer, Jacob
通讯作者：
Rajfer, Jacob
影响因子：
2.6
作者：
Kovanecz, I.;Rambhatla, A.;Gonzalez-Cadavid, N.
通讯作者：
Gonzalez-Cadavid, N.