Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Am J Med Sci. 2012 Jun;343(6):458-61. doi: 10.1097/MAJ.0b013e318235b03e.
Obstructive sleep apnea (OSA) is an independent risk factor of multisystem injury including liver and cardiovascular system. Chronic intermittent hypoxia (CIH) associated with recurrent apneas in patients with OSA is one of the most important causes of the increased various systems injury and oxidative stress induced by CIH is an important pathogenic mechanism. Reports indicated that females are less susceptible to oxidative stress injury. The goal of this study was to explore if there exists gender deference of thioredoxin system (Trx/Txnip) alterations by CIH and to clarify a clue for studying gender disparity of OSA-related multisystem injury. C57BL/6J mice of each gender were exposed to CIH with a fractional inspired O2 (FiO2) nadir of 5%. The oxidative and antioxidant biomarkers were evaluated, including serum OxLDL level and Trx/Txnip expression of liver tissue. Male mice exposed to CIH exhibited significant increases in serum OxLDL level than that of the male control (73.24 ± 22.43 μg/dL, 45.20 ± 28.53 μg/dL, P = 0.032) but no significant difference in the females. Male mice exposed to CIH also exhibited decreased expression of Trx than the female (0.4460 ± 0.1023 versus 1.0454 ± 0.1777, P = 0.013) and increased expression of Txnip than the female (0.0123 ± 0.0476 versus 0.0065 ± 0.0058, P = 0.022). These data suggest that CIH induces thioredoxin system change in a gender-specific fashion in mice.
阻塞性睡眠呼吸暂停（OSA）是多系统损伤的独立危险因素，包括肝脏和心血管系统。与 OSA 患者反复呼吸暂停相关的慢性间歇性低氧（CIH）是导致各种系统损伤增加的最重要原因之一，而 CIH 诱导的氧化应激是一个重要的发病机制。有报道称，女性对氧化应激损伤的敏感性较低。本研究旨在探讨 CIH 是否存在性别差异导致硫氧还蛋白系统（Trx/Txnip）改变，并为研究 OSA 相关多系统损伤的性别差异提供线索。各性别 C57BL/6J 小鼠分别暴露于 FiO2 下限时为 5%的 CIH。评估氧化和抗氧化生物标志物，包括血清 OxLDL 水平和肝组织 Trx/Txnip 表达。与雄性对照组相比，雄性 CIH 暴露小鼠的血清 OxLDL 水平显著升高（73.24 ± 22.43 μg/dL，45.20 ± 28.53 μg/dL，P = 0.032），但雌性小鼠无显著差异。与雌性相比，雄性 CIH 暴露小鼠的 Trx 表达降低（0.4460 ± 0.1023 比 1.0454 ± 0.1777，P = 0.013），Txnip 表达升高（0.0123 ± 0.0476 比 0.0065 ± 0.0058，P = 0.022）。这些数据表明，CIH 以性别特异性的方式诱导小鼠的硫氧还蛋白系统发生改变。
