摘要
勃起功能障碍(ED)和慢性肾衰竭(CRF)之间的关系已在几个研究中被报道。本研究旨在探讨长期使用西地那非是否能增强CRF诱导大鼠的勃起能力。此外,我们评估了该治疗对某些分子的影响,这些分子被认为在勃起生理学及CRF相关的ED中起关键作用。研究分三组:(1)年龄配对的对照组,(2)CRF诱导的大鼠模型组,(3)CRF诱导大鼠给予西地那非慢性给药组((5 mg /kg口服6周[CRF诱导后6周开始治疗])。 3个月时,所有的动物进行海绵体神经刺激(CNS)来评估勃起功能。在所有大鼠组进行,阴茎组织晚期糖化终产物(AGE的) / 5-羟甲基-2-糠醛,丙二醛(MDA),cGMP(ELISA),诱导型一氧化氮合酶(iNOS)和神经元型NOS(nNOS的)(Western印迹)分析。CRF诱导大鼠与对照组相比,勃起功能有显著降低(P 〈0.05)。CRF诱导大鼠西地那非治疗组(第3组),海绵体内压(ICP)和曲线下面积的
增加量,大于CRF诱导大鼠组(第2组)。此外,西地那非治疗下调了AGE,MDA和iNOS的水平,同时保持了CRF诱导阴茎组织的nNOS和cGMP含量。西地那非治疗组AGE,MDA,iNOS的下降和nNOS,cGMP水平的增加,增加了ICP和海绵体神经刺激(CNS)的总ICP,使得CRF诱导大鼠阴茎勃起功能得到改善。本研究的结果表明慢性西地那非给药对CRF诱导大鼠的勃起功能有治疗效果。
The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg^-1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P 〈 0.05). The increase in both intracavernosal pressure (ICP) and area under the curve of CRF-induced rats treated with sildenafil (Group 3) was greater than CRF-induced rats (Group 2). Additionally, sildenafil treatment decreased AGE, MDA and iNOS levels, while it preserved nNOS and cGMP contents in CRF-induced penile tissue. Decreased AGE, MDA, iNOS and increased nNOS, cGMP levels at the sildenafil-treated group increased both ICP and Total ICP to CNS, which led to improve erectile function in CRF-induced rats. The results of the present study revealed the therapeutic effect of chronic sildenafil administration on erectile function in CRF-induced rats.