Chronic Administration of Sildenafil Modified the Impaired VEGF System and Improved the Erectile Function in Rats with Diabetic Erectile Dysfunction
Chronic Administration of Sildenafil Modified the Impaired VEGF System and Improved the Erectile Function in Rats with Diabetic Erectile Dysfunction
复制标题
长期服用西地那非可改善糖尿病性勃起功能障碍大鼠受损的 VEGF 系统并改善勃起功能
DOI：
10.1111/j.1743-6109.2010.01844.x
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发表时间：
2010-12-01
影响因子：
3.5
通讯作者：
Deng, Chunhua
中科院分区：
文献类型：
--
作者：
Liu, Guihua;Sun, Xiangzhou;Deng, Chunhua
糖尿病勃起功能障碍（DMED）是血管内皮功能障碍的结果. DMED患者常伴有磷酸二酯酶5型抑制剂治疗的疗效降低。目的：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，并改善糖尿病勃起功能障碍大鼠的勃起功能。方法：一组Sprague道利大鼠（n = 30）通过腹腔注射链脲佐菌素诱导DMED（40 mg/kg）并通过皮下注射阿扑吗啡（100 mg/kg）筛选。然后，他们暴露于车辆或西地那非（在我们的医院，分别为5 mg/kg和10 mg/kg）10周。另外一个非糖尿病和年龄匹配的对照组（n = 10）也被分配，并给予常规饮食相同的时期。在西地那非末次给药后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）、阴茎组织形态学、免疫组织学分析和VEGF、VEGFR 1和eNOS蛋白质印迹分析。主要结果指标：慢性西地那非对阴茎结构的功能、形态学和蛋白质组学的影响结果：与对照组相比，模型组大鼠颅内压（ICP）、ICP/MAP比值、与未接受西地那非的DMED大鼠相比，在接受西地那非（分别为5 mg/kg和10 mg/kg）的两个组中观察到曲线下面积。阴茎组织的免疫组织化学染色显示，与长期西地那非给药组的改善相比，对照组的VEGF、VEGFR 1和eNOS染色减少。Western blot分析表明完全相同的results.Conclusion.We表明，每日西地那非管理可以恢复受损的VEGF系统在DMED大鼠的阴茎，并逐步改善勃起功能和内皮功能，这表明通过VEGF/eNOS信号级联改善信号的潜在的一般机制。Liu G，Sun X，Dai Y，Zheng F，Wang D，Huang Y，Bian J，and Deng C.长期给予西地那非可改善糖尿病勃起功能障碍大鼠受损的VEGF系统并改善勃起功能。J Sex Med 2010;7：3868-3878.
Introduction.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.Aim.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.Methods.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.Main Outcome Measure.Functional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined.Results.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.Conclusion.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. Liu G, Sun X, Dai Y, Zheng F, Wang D, Huang Y, Bian J, and Deng C. Chronic administration of sildenafil modified the impaired VEGF system and improved the erectile function in rats with diabetic erectile dysfunction. J Sex Med 2010;7:3868-3878.