细胞外信号调节激酶在间断缺氧导致大鼠勃起功能障碍中的调控作用

Obstructive sleep apnea syndrome (OSAS), a highly prevalent breathing disorder in sleep, characterized by chronic intermittent hypoxia (CIH), has emerged as an independent risk factor for erectile dysfunction (ED), and the frequency and severity of ED appear to correlate with the severity of OSAS. However, limited information exists regarding the pathophysiologic basis of ED in OSAS. Previous in vivo study from our laboratory has demonstrated that increased nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) -derived reactive oxygen species (ROS) is a major cause for ED after 6 weeks of CIH, while a NADPH oxidase inhibitor treatment blocks CIH-associated ROS generation and can subsequently preserve erectile function. Accumulated evidence implicates the apnea-related multiple cycles of hypoxia / reoxygenation in promoting the formation of ROS and inducing oxidative stress. Recent studies have revealed that cellular signaling pathways are regulated by the intracellular redox state. Generation of ROS leads to the activation of protein tyrosine kinase, and this is followed by the stimulation of downstream signaling systems, including the extracellular signal regulated kinase (ERK). Continually overproduced ROS, especially superoxide anion（O2-）production, will eventually cause a change in redox signaling to active the ERK pathway. However, there is no available evidence indicating whether ROS productions alter the expression of ERK in the CIH rat penis. Therefore, in the present study, we determined whether NADPH oxidase-derived ROS productions regulate the expression of ERK in the CIH rat penis and whether ERK play significant roles in the pathogenesis of CIH-associated ED.

阻塞性睡眠呼吸暂停综合征（OSAS）是一种常见疾病，在成年人中的发病率为1%-5%，甚至更高。OSAS患者由于反复发作的低氧血症、神经内分泌改变、微觉醒等，可导致全身各个系统的损伤，包括勃起功能障碍。由于OSAS患者最重要一个病理生理特点是夜间睡眠时反复的缺氧-复氧，即间断缺氧。所以，我们前期的研究选用慢性间歇缺氧大鼠模型，发现慢性间断缺氧可导致大鼠勃起功能障碍，而还原型辅酶Ⅱ氧化酶（NADPH oxidase）的活化在其中发挥了重要的作用：间断缺氧导致大鼠体内NADPH oxidase活性增加，进而导致活性氧（ROS）的增加，最终导致了大鼠勃起功能的障碍。然而，ROS是通过怎样的机制导致的勃起功能障碍，尚未阐明。本研究旨在探讨细胞外信号调节激酶（ERK）是否作为ROS的下游信号通路在间断缺氧导致大鼠勃起功能障碍中发挥重要的作用，从而为进一步的临床试验提供理论依据。