NADPH Oxidase Activation: A Mechanism of Erectile Dysfunction in a Rat Model of Sleep Apnea
NADPH Oxidase Activation: A Mechanism of Erectile Dysfunction in a Rat Model of Sleep Apnea
复制标题
NADPH 氧化酶激活：睡眠呼吸暂停大鼠模型勃起功能障碍的机制
DOI：
10.2164/jandrol.112.016642
复制
发表时间：
2012-11-01
影响因子：
--
通讯作者：
Liu, Hui-Guo
中科院分区：
文献类型：
--
作者：
Liu, Kui;Liu, Xian-Sheng;Liu, Hui-Guo
勃起功能障碍（艾德）是阻塞性睡眠呼吸暂停综合征（OSAS）男性患者的常见并发症。长期间歇性缺氧（LTIH）是OSAS的标志之一，可介导ED。本研究的目的是验证大鼠对LTIH的反应中烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶活性增加导致艾德的假设。健康雄性SD大鼠随机分为4组：LTIH组、夹竹桃素（一种选择性NADPH氧化酶抑制剂）治疗LTIH组、假LTIH组和夹竹桃素治疗假组。通过测量电刺激海绵体神经时的平均动脉压（MAP）和海绵体内压（ICP）来检查勃起功能。采用实时定量聚合酶链反应和蛋白质印迹法检测海绵体（CC）中NADPH氧化酶亚基的mRNA和蛋白质表达。采用比色法测定丙二醛和超氧化物歧化酶的含量。一氧化氮合酶（NOS）亚型在CC也进行了研究。LTIH显着减弱勃起反应（ICP/MAP），这些都是部分防止夹竹桃麻素治疗。促进氧化应激相关的NADPH氧化酶亚基激活被发现在CC从LTIH大鼠。在LTIH大鼠中观察到组成型NOS（cNOS）的表达和活性降低，包括内皮型NOS和神经型NOS，与诱导型NOS（iNOS）的表达和活性增强相关。夹竹桃麻素可防止LTIH大鼠cNOS活性的下降，并抑制iNOS的表达和活性。这些结果表明，NADPH氧化酶激活在LTIH介导的ED的发病机制中起重要作用。
Erectile dysfunction (ED) is a frequent occurrence in male patients with obstructive sleep apnea syndrome (OSAS). Long-term intermittent hypoxia (LTIH), one of the hallmarks of OSAS, could mediate ED. The objective of this study was to test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to ED in rat responses to LTIH. Healthy male Sprague-Dawley rats were randomly distributed into 4 groups: a LTIH group, an apocynin (a selective NADPH oxidase inhibitor)-treated LTIH group, a sham LTIH group, and an apocynin-treated sham group. Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) on electrical stimulation of the cavernous nerve. Real-time quantitative polymerase chain reaction and Western blot were used to examine mRNA and protein expression of NADPH oxidase subunit in corpus cavernosa (CC). The level of malondialdehyde and superoxide dismutase were detected by colorimetry. Nitric oxide synthase (NOS) isoforms in CC were also investigated. LTIH markedly attenuated the erectile responses (ICP/MAP), and these were partially prevented by apocynin treatment. Promoted oxidative stress associated NADPH oxidase subunit activation was found in CC from LTIH rats. Decreased expression and activity of constitutive NOS (cNOS), including endothelial NOS and neuronal NOS, associated with enhanced inducible NOS (iNOS) expression and activity were observed in LTIH rats. Apocynin prevented the decrease in cNOS activity and inhibited iNOS expression and activity in LTIH rats. These results indicate that NADPH oxidase activation plays an important role in the pathogenesis of LTIH-mediated ED.