Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat
Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat
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DOI：
10.1016/j.urology.2006.05.011
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发表时间：
2006-08-01
期刊：
影响因子：
2.1
通讯作者：
Rajfer, Jacob
中科院分区：
文献类型：
--
作者：
Ferrini, Monica G.;Davila, Hugo H.;Rajfer, Jacob
目标。阳萎，特别是躯体静脉闭塞功能障碍(CVOD)，发生在根治性前列腺切除术后。它是由海绵体神经损伤引起的，导致海绵体内平滑肌(SM)丧失和胶原增加。最近的报道表明，前列腺癌根治术后长期应用磷酸二酯酶-5抑制剂可能会阻止这种改变。我们的目的是确定大鼠双侧海绵体神经切除(BCNX)是否导致CVOD，以及长期抑制磷酸二酯酶-5是否改善这些组织学和功能损害。大鼠(n=7~11只/组)接受假手术、BCNX或BCNX+饮水中的伐地那非(30 mg/L)。45d后处死大鼠，用动态灌注海绵体测定法测定CVOD。采用组织化学/免疫组织化学方法，定量图像分析SM/胶原比值、III型胶原/I型胶原比值、α-SM肌动蛋白、诱导型一氧化氮合酶(NOS)、增殖细胞核抗原和末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷缺口末端标记作为细胞凋亡的标志物。与假手术组相比，BCNX组大鼠心脏血管密度下降，SM/胶原比值降低60%，一氧化氮合酶表达增加一倍，体内细胞凋亡率增加三倍。与BCNX组相比，伐地那非增加了NOS和增殖细胞核抗原的表达(SM细胞复制)，并使动态输注海绵体下降率和SM/胶原比值正常化。长期应用伐地那非可能通过保护SM含量和抑制小体纤维化而预防前列腺癌根治术后CVOD，其机制可能与其对NOS的影响有关。
Objectives. 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.Methods. 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 (NOS), proliferating cell nuclear antigen, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling as a marker of apoptosis.Results. 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 NOS expression, and a threefold increase in intracorporeal apoptosis. Compared with the BCNX group, vardenafil increased both NOS and proliferating cell nuclear antigen expression (SM cell replication), with normalization of the dynamic infusion cavernosometry drop rate and SM/collagen ratio.Conclusions. Long-term treatment with vardenafil may prevent CVOD after radical prostatectomy by preserving SM content and inhibiting corporal fibrosis possibly by its effect on NOS.