Ferrini Monica G, Davila Hugo H, Kovanecz Istvan, Sanchez Sandra P, Gonzalez-Cadavid Nestor F, Rajfer Jacob
Department of Urology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA.
Urology. 2006 Aug;68(2):429-35. doi: 10.1016/j.urology.2006.05.011.
Impotence, specifically corporal veno-occlusive dysfunction (CVOD), occurs after radical prostatectomy. It results from the effects of cavernosal nerve damage, which causes smooth muscle (SM) loss and an increase in collagen within the corpora. Recent reports have suggested that long-term treatment with phosphodiesterase-5 inhibitors after radical prostatectomy may prevent such changes. We aimed to determine whether bilateral cavernosal nerve resection (BCNX) in the rat leads to CVOD and whether long-term phosphodiesterase-5 inhibition ameliorates these histologic and functional impairments.
Rats (n = 7 to 11/group) underwent either the sham operation, BCNX, or BCNX plus 30 mg/L vardenafil in the drinking water. Before the rats were killed 45 days later, CVOD was assessed by dynamic infusion cavernosometry. The corpora underwent histochemistry/immunohistochemistry with quantitative image analysis for SM/collagen ratio, collagen III/I ratio, alpha-SM actin, inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling as a marker of apoptosis.
Compared with the sham group, the BCNX rats demonstrated CVOD as measured by the drop rate, a 60% reduction in the SM/collagen ratio, a twofold increase in iNOS expression, and a threefold increase in intracorporeal apoptosis. Compared with the BCNX group, vardenafil increased both iNOS and proliferating cell nuclear antigen expression (SM cell replication), with normalization of the dynamic infusion cavernosometry drop rate and SM/collagen ratio.
Long-term treatment with vardenafil may prevent CVOD after radical prostatectomy by preserving SM content and inhibiting corporal fibrosis possibly by its effect on iNOS.
阳痿,特别是海绵体静脉闭塞功能障碍(CVOD),发生于根治性前列腺切除术后。它是由海绵体神经损伤所致,会引起平滑肌(SM)丢失及海绵体内胶原蛋白增加。近期报道表明,根治性前列腺切除术后长期使用磷酸二酯酶-5抑制剂可能预防此类变化。我们旨在确定大鼠双侧海绵体神经切除(BCNX)是否会导致CVOD,以及长期磷酸二酯酶-5抑制是否能改善这些组织学和功能损害。
将大鼠(每组n = 7至11只)分为三组,分别接受假手术、BCNX或BCNX加饮水中含30 mg/L伐地那非处理。45天后处死大鼠前,通过动态灌注海绵体测压评估CVOD。对海绵体进行组织化学/免疫组织化学检查,并通过定量图像分析测定SM/胶原蛋白比值、胶原蛋白III/I比值、α-SM肌动蛋白、诱导型一氧化氮合酶(iNOS)、增殖细胞核抗原以及作为细胞凋亡标志物的末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记。
与假手术组相比,BCNX大鼠表现出CVOD,表现为灌注速率下降、SM/胶原蛋白比值降低60%、iNOS表达增加两倍以及体内细胞凋亡增加三倍。与BCNX组相比,伐地那非增加了iNOS和增殖细胞核抗原的表达(SM细胞增殖),动态灌注海绵体测压灌注速率和SM/胶原蛋白比值恢复正常。
长期使用伐地那非可能通过保留SM含量并可能通过其对iNOS的作用抑制海绵体纤维化,从而预防根治性前列腺切除术后的CVOD。