La Vignera Sandro, Condorelli Rosita, Vicari Enzo, D'Agata Rosario, Calogero Aldo E
Section of Endocrinology, Andrology, and Internal Medicine, Department of Internal Medicine and Systemic Diseases, Catania University, Policlinico G. Rodolico, S Sofia 78th St, Bldg 4, Rm 2C82, 95123 Catania, Italy.
J Androl. 2012 Mar-Apr;33(2):170-5. doi: 10.2164/jandrol.111.013342. Epub 2011 May 5.
This study evaluated the effects of a chronic treatment with tadalafil, a specific phosphodiesterase V inhibitor, on endothelial apoptosis through changes in the serum concentration of endothelial microparticles (EMP). EMPs were arbitrarily chosen as a marker of endothelial apoptosis, and the changes in their concentration were monitored before and after treatment. Additionally, administration of endothelial antioxidant compound (EAC) during the follow-up, after discontinuation of tadalafil, was evaluated to determine whether this treatment improved the potential effects of tadalafil on the endothelium. Seventy-five patients with arterial erectile dysfunction were evaluated at baseline and after administration of tadalafil (5 mg once daily for 90 days). The International Index of Erectile Function questionnaire was administered, and penile dynamic Doppler and flow-cytometric (serum concentrations of EMPs) analyses were performed before (T0) and after treatment. Time points after tadalafil discontinuation: T1, after 1 week; T2, after 3 months; and T3, after 6 months. Three different schemes of follow-up were evaluated: group A, follow-up with EAC administration, after tadalafil discontinuation, for 6 months; group B, follow-up without other treatment; and group C, follow-up with placebo during the follow-up, after tadalafil cessation. The events CD45(neg)/CD144(pos)/annexinV(pos) were defined EMPs. Patients treated with tadalafil showed a significant decrease in serum EMPs 1 week after discontinuing tadalafil (16.4% ± 3.6% vs 7.1% ± 3.3%). This effect was maintained for up to 3 months in the group without other treatment during follow-up and was maintained for up to 6 months in the group treated with EAC during follow-up. Chronic treatment with tadalafil reduces endothelial apoptosis in patients with arterial erectile dysfunction. Further, EAC treatment prolongs and stabilizes the duration of antiapoptotic effects on the endothelium that are initially promoted by tadalafil treatment.
本研究通过内皮微粒（EMP）血清浓度的变化，评估了特异性磷酸二酯酶V抑制剂他达拉非的长期治疗对内皮细胞凋亡的影响。任意选择EMP作为内皮细胞凋亡的标志物，并在治疗前后监测其浓度变化。此外，在停用他达拉非后的随访期间给予内皮抗氧化化合物（EAC），以确定这种治疗是否能改善他达拉非对内皮的潜在作用。对75例动脉性勃起功能障碍患者在基线期及给予他达拉非（每日1次，5mg，共90天）后进行评估。在治疗前（T0）和治疗后进行国际勃起功能指数问卷调查，并进行阴茎动态多普勒和流式细胞术（EMP血清浓度）分析。他达拉非停药后的时间点：T1，1周后；T2，3个月后；T3，6个月后。评估了三种不同的随访方案：A组，在停用他达拉非后给予EAC随访6个月；B组，不进行其他治疗的随访；C组，在停用他达拉非后随访期间给予安慰剂。事件CD45(neg)/CD144(pos)/膜联蛋白V(pos)被定义为EMP。接受他达拉非治疗的患者在停用他达拉非1周后血清EMP显著降低（16.4%±3.6%对7.1%±3.3%）。在随访期间不进行其他治疗的组中，这种效果维持长达3个月，而在随访期间接受EAC治疗的组中维持长达6个月。他达拉非的长期治疗可减少动脉性勃起功能障碍患者的内皮细胞凋亡。此外，EAC治疗可延长并稳定他达拉非治疗最初促进的对内皮的抗凋亡作用的持续时间。
