Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA.
J Sex Med. 2011 Nov;8(11):3086-97. doi: 10.1111/j.1743-6109.2011.02442.x. Epub 2011 Aug 24.
Erectile dysfunction is a serious and common complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for the penile erection.
The goal of the present study was to determine the impact of exercise training (ExT) on the centrally mediated erectile dysfunction in streptozotocin (STZ)-induced type I diabetic (T1D) rats.
Male Sprague-Dawley rats were injected with STZ to induce diabetes mellitus. Three weeks after STZ or vehicle injections, rats were assigned to either ExT (treadmill running for 3-4 weeks) or sedentary groups to produce four experimental groups: control + sedentary, T1D + sedentary, control + ExT, and T1D + ExT.
After 3-4 weeks ExT, central N-methyl-D-aspartic acid (NMDA) or sodium nitroprusside (SNP)-induced penile erectile responses were measured. Neuronal nitric oxide synthase (nNOS) expression in the paraventricular nucleus (PVN) of the hypothalamus was measured by using histochemistry, real time polymerase chain reaction (PCR) and Western blot approaches.
In rats with T1D, ExT significantly improved the blunted erectile response, and the intracavernous pressure changes to NMDA (50 ng) microinjection within the PVN (T1D + ExT: 3.0 ± 0.6 penile erection/rat; T1D + sedentary: 0.5 ± 0.3 penile erection/rat within 20 minutes, P < 0.05). ExT improved erectile dysfunction induced by central administration of exogenous nitric oxide (NO) donor, SNP in T1D rats. Other behavior responses including yawning and stretching, induced by central NMDA and SNP microinjection were also significantly increased in T1D rats after ExT. Furthermore, we found that ExT restored the nNOS mRNA and protein expression in the PVN in T1D rats.
These results suggest that ExT may have beneficial effects on the erectile dysfunction in diabetes through improvement of NO bioavailability within the PVN. Thus, ExT may be used as therapeutic modality to up-regulate nNOS within the PVN and improve the central component of the erectile dysfunction in diabetes mellitus.
勃起功能障碍是糖尿病的一种严重且常见的并发症。除了外周作用外,中枢机制也与阴茎勃起有关。
本研究旨在确定运动训练(ExT)对链脲佐菌素(STZ)诱导的 1 型糖尿病(T1D)大鼠中枢介导的勃起功能障碍的影响。
雄性 Sprague-Dawley 大鼠注射 STZ 诱导糖尿病。STZ 或载体注射后 3 周,大鼠被分配到运动组(跑步机跑步 3-4 周)或安静组,产生 4 个实验组:对照组+安静组、T1D+安静组、对照组+ExT 和 T1D+ExT。
经过 3-4 周的 ExT,测量中枢 N-甲基-D-天冬氨酸(NMDA)或硝普钠(SNP)诱导的阴茎勃起反应。通过组织化学、实时聚合酶链反应(PCR)和 Western blot 方法测量下丘脑室旁核(PVN)中的神经元型一氧化氮合酶(nNOS)表达。
在 T1D 大鼠中,ExT 显著改善了勃起反应减弱的情况,并且 NMDA(50ng)在 PVN 内微注射后的阴茎内压变化(T1D+ExT:3.0±0.6 次勃起/大鼠;T1D+安静组:20 分钟内 0.5±0.3 次勃起/大鼠,P<0.05)。ExT 改善了 T1D 大鼠中枢给予外源性一氧化氮(NO)供体 SNP 引起的勃起功能障碍。在 T1D 大鼠中,ExT 后,中枢 NMDA 和 SNP 微注射引起的打哈欠和伸展等其他行为反应也显著增加。此外,我们发现 ExT 恢复了 T1D 大鼠 PVN 中的 nNOS mRNA 和蛋白表达。
这些结果表明,ExT 可能通过提高 PVN 内的 NO 生物利用度对糖尿病引起的勃起功能障碍产生有益影响。因此,ExT 可作为治疗方式,上调 PVN 中的 nNOS,改善糖尿病勃起功能障碍的中枢成分。