Department of Urology, First Affiliated Hospital of Sun Yet-Sen University, Guangzhou, China.
J Sex Med. 2010 Dec;7(12):3868-78. doi: 10.1111/j.1743-6109.2010.01844.x.
Men frequently develop diabetic erectile dysfunction (DMED), as a result of endothelial dysfunction. DMED patients often have reduced efficacy with phosphodiesterase type 5 inhibitors therapy.
To determine whether chronic sildenafil administration can modify the impaired vascular endothelial growth factor (VEGF) system and improve the erectile function in rats with diabetic erectile dysfunction.
A group of Sprague Dawley rats (n = 30) with DMED were induced by intraperitoneal injection of streptozotocin (40 mg/kg) and screened by subcutaneous injection of Apomorphine (100 mg/kg). They were then exposed to either vehicle or sildenafil (prescribed in our hospital, 5 mg/kg and 10 mg/kg, respectively) for 10 weeks. An additional nondiabetic and age-matched control group (n = 10) was also allocated and given the routine diet for the same period. Assessments were performed to both groups at 36 hours after the last dose of sildenafil. Penile intracavernous pressure (ICP), mean arterial pressure (MAP), penile tissue morphology, immunohistologic analysis, and Western blot analysis of VEGF, VEGFR1, and eNOS were determined.
Functional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined.
A significant increase of ICP, ICP/MAP ratio, and area under the curve were observed in the both groups treated by sildenafil (5 mg/kg and 10 mg/kg, respectively), compared with the DMED rats without receiving Sildenafil. Immunohistochemical staining of their penile tissue showed a decrease in VEGF, VEGFR1, and eNOS staining in the controlled group compared with an improvement in the chronic sildenafil administration group. Western blot analysis demonstrated exactly the same results.
We demonstrated that daily sildenafil administration can restore the impaired VEGF system in the penis of DMED rats and progressively improve both erectile function and endothelial function, suggesting a potential general mechanism of improved signaling through the VEGF/eNOS signaling cascade.
男性常因血管内皮功能障碍而出现糖尿病性勃起功能障碍（DMED）。DMED 患者对磷酸二酯酶 5 抑制剂治疗的疗效往往较低。
确定慢性西地那非给药是否可以改变受损的血管内皮生长因子（VEGF）系统并改善糖尿病性勃起功能障碍大鼠的勃起功能。
一组患有 DMED 的 Sprague Dawley 大鼠（n = 30）通过腹腔注射链脲佐菌素（40 mg/kg）诱导，并用皮下注射阿扑吗啡（100 mg/kg）筛选。然后，它们分别暴露于载体或西地那非（我院处方，分别为 5mg/kg 和 10mg/kg）10 周。还分配了一个额外的非糖尿病和年龄匹配的对照组（n = 10），并在同一时期给予常规饮食。在最后一次西地那非给药后 36 小时对两组进行评估。测定阴茎海绵体内压（ICP）、平均动脉压（MAP）、阴茎组织形态、免疫组织化学分析和 VEGF、VEGFR1 和 eNOS 的 Western blot 分析。
通过慢性西地那非（分别为 5mg/kg 和 10mg/kg）给药确定阴茎结构的功能、形态和蛋白质组变化。
与未接受西地那非治疗的 DMED 大鼠相比，两组接受西地那非（5mg/kg 和 10mg/kg）治疗的大鼠 ICP、ICP/MAP 比值和曲线下面积均显著增加。与对照组相比，其阴茎组织的免疫组织化学染色显示 VEGF、VEGFR1 和 eNOS 染色减少，而慢性西地那非给药组则有所改善。Western blot 分析也得出了完全相同的结果。
我们证明，每日西地那非给药可以恢复 DMED 大鼠阴茎中受损的 VEGF 系统，并逐渐改善勃起功能和内皮功能，提示通过 VEGF/eNOS 信号级联改善信号传递的潜在一般机制。
