Assessment of Androgen Replacement Therapy for Erectile Function in Rats with Type 2 Diabetes Mellitus by Examining Nitric Oxide-Related and Inflammatory Factors
Assessment of Androgen Replacement Therapy for Erectile Function in Rats with Type 2 Diabetes Mellitus by Examining Nitric Oxide-Related and Inflammatory Factors
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DOI：
10.1111/jsm.12447
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发表时间：
2014-04-01
影响因子：
3.5
通讯作者：
Kimura, Kazunori
中科院分区：
文献类型：
--
作者：
Kataoka, Tomoya;Hotta, Yuji;Kimura, Kazunori
2型糖尿病（T2DM）已成为一个主要的公共卫生问题，被认为是勃起功能障碍（ED）的危险因素。2型糖尿病还与雄激素缺乏有关。然而，在T2DM动物模型中，雄激素替代疗法（ART）治疗ED的基础研究很少，ART治疗T2DM诱导ED的机制尚不清楚。目的通过检测炎症和一氧化氮（NO）相关因子，探讨ART对T2DM大鼠ED的影响。方法将大鼠（Long-Evans Tokushima Fatty， OLETF）和对照组（Long-Evans Tokushima Otsuka， LETO）分为LETO组、OLETF组和ART组。在ART组，OLETF大鼠从20 ~ 25周龄每天注射睾酮（3mg/kg/天，皮下注射）；LETO和OLETF大鼠只接受载具。我们通过电刺激海绵体神经后测量海绵体内压（ICP）和平均动脉压（MAP）的比值来测量勃起功能，并在等长张力研究中评估海绵体的内皮功能。采用聚合酶链反应检测内皮细胞NO合成酶（eNOS）、诱导型NO合成酶（iNOS）、sirtuin-1 （Sirt1）、白细胞介素-6 （IL-6）、肿瘤坏死因子α (TNF-) mRNA的表达。结果OLETF组ICP/MAP比值明显降低，ART组ICP/MAP比值明显提高（P . 491）
IntroductionType 2 diabetes mellitus (T2DM) has become a major public health issue and is considered a risk factor for erectile dysfunction (ED). T2DM is also associated with androgen deficiency. However, there have been few basic studies on androgen replacement therapy (ART) for ED treatment in T2DM animal models, and the mechanism underlying the effect of ART on T2DM-induced ED is unclear.AimTo investigate the effect of ART on ED in T2DM rats by examining inflammatory and nitric oxide (NO)-related factors.MethodsOtsuka Long-Evans Tokushima Fatty (OLETF) rats and their controls, Long-Evans Tokushima Otsuka (LETO) rats, were distributed into three groups: LETO, OLETF, and ART. In the ART group, OLETF rats were treated daily with testosterone (3mg/kg/day, subcutaneously) from 20 to 25 weeks of age; LETO and OLETF rats received vehicle only.Main Outcome MeasuresWe measured erectile function by using measurements of the ratio between intracavernosal pressure (ICP) and mean arterial pressure (MAP) following electrical stimulation of the cavernous nerve and by evaluating the endothelial function of the corpus cavernosum in an isometric tension study. Expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), sirtuin-1 (Sirt1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-) mRNA was detected using polymerase chain reaction.ResultsThe ICP/MAP ratio in the OLETF group was significantly decreased and that in the ART group was significantly improved (P