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Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis

机译:通过重复给药udenafil在化学性糖尿病形成大鼠模型中提高海绵体中一氧化氮合酶基因和蛋白的表达

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摘要

Erectile dysfunction (ED) is a major complication of diabetes mellitus (DM). This study investigates the relationship between ED and the downregulation of constitutive nitric oxide synthase (cNOS) in the corpus cavernosum (CC) of diabetic rats. It also examines the effects of udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on ED and cNOS expression levels. After 16 weeks of daily oral treatment with udenafil in diabetic rats, the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio was recorded to measure erectile function, and cNOS expression was measured using reverse transcriptase (RT)-PCR and immunoblots. Although the ICP/MAP ratio and the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in the CC were markedly decreased in diabetic rats, long-term udenafil treatment improved the erectile function and increased cNOS expression compared with diabetic controls. These findings suggest that ED in DM is closely related to decreased cNOS expression in the CC and that udenafil has the ability to compensate for this pathological change by modulating cNOS expression. Udenafil also has an inhibitory role in cGMP (cyclic guanosine monophosphate) degradation.
机译:勃起功能障碍(ED)是糖尿病(DM)的主要并发症。本研究探讨了糖尿病与糖尿病大鼠海绵体(CC)组成型一氧化氮合酶(cNOS)下调之间的关系。它还检查了5型磷酸二酯酶(PDE5)抑制剂udenafil对ED和cNOS表达水平的影响。在糖尿病大鼠中每天口服udenafil 16周后,记录海绵体内压力/平均动脉压(ICP / MAP)比率以测量勃起功能,并使用逆转录酶(RT)-PCR和免疫印迹法测量cNOS表达。尽管在糖尿病大鼠中CC的ICP / MAP比和内皮NOS(eNOS)和神经元NOS(nNOS)的表达水平均明显降低,但与糖尿病对照组相比,长期的udenafil治疗可改善勃起功能并增加cNOS表达。这些发现表明,DM中的ED与CC中cNOS表达的降低密切相关,并且udenafil具有通过调节cNOS表达来补偿这种病理变化的能力。乌地那非在cGMP(环鸟苷一磷酸)降解中也具有抑制作用。

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