Faculty of Medicine, Department of Internal Medicine III, Osaka Medical College, Takatsuki, Osaka, Japan.
Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H1062-9. doi: 10.1152/ajpheart.00150.2011. Epub 2011 Jun 3.
Sleep apnea syndrome increases the risk of cardiovascular morbidity and mortality. We previously reported that intermittent hypoxia increases superoxide production in a manner dependent on nicotinamide adenine dinucleotide phosphate and accelerates adverse left ventricular (LV) remodeling. Recent studies have suggested that hydrogen (H(2)) may have an antioxidant effect by reducing hydroxyl radicals. In this study, we investigated the effects of H(2) gas inhalation on lipid metabolism and LV remodeling induced by intermittent hypoxia in mice. Male C57BL/6J mice (n = 62) were exposed to intermittent hypoxia (repetitive cycle of 1-min periods of 5 and 21% oxygen for 8 h during daytime) for 7 days. H(2) gas (1.3 vol/100 vol) was given either at the time of reoxygenation, during hypoxic conditions, or throughout the experimental period. Mice kept under normoxic conditions served as controls (n = 13). Intermittent hypoxia significantly increased plasma levels of low- and very low-density cholesterol and the amount of 4-hydroxy-2-nonenal-modified protein adducts in the LV myocardium. It also upregulated mRNA expression of tissue necrosis factor-α, interleukin-6, and brain natriuretic peptide, increased production of superoxide, and induced cardiomyocyte hypertrophy, nuclear deformity, mitochondrial degeneration, and interstitial fibrosis. H(2) gas inhalation significantly suppressed these changes induced by intermittent hypoxia. In particular, H(2) gas inhaled at the timing of reoxygenation or throughout the experiment was effective in preventing dyslipidemia and suppressing superoxide production in the LV myocardium. These results suggest that inhalation of H(2) gas was effective for reducing oxidative stress and preventing LV remodeling induced by intermittent hypoxia relevant to sleep apnea.
睡眠呼吸暂停综合征增加了心血管发病率和死亡率的风险。我们之前报道过，间歇性低氧会增加超氧化物的产生，这种产生方式依赖于烟酰胺腺嘌呤二核苷酸磷酸，并加速左心室（LV）的不良重构。最近的研究表明，氢气（H2）通过减少羟基自由基可能具有抗氧化作用。在这项研究中，我们研究了 H2 气体吸入对间歇低氧诱导的小鼠脂质代谢和 LV 重构的影响。雄性 C57BL/6J 小鼠（n = 62）暴露于间歇低氧（白天 8 小时内重复进行 5%和 21%氧气 1 分钟的周期）7 天。H2 气体（1.3 体积/100 体积）在复氧时、在低氧条件下或整个实验期间给予。在常氧条件下饲养的小鼠作为对照（n = 13）。间歇低氧显著增加了血浆中低和极低密度胆固醇的水平以及 LV 心肌中 4-羟基-2-壬烯醛修饰蛋白加合物的数量。它还上调了组织坏死因子-α、白细胞介素-6 和脑钠肽的 mRNA 表达，增加了超氧化物的产生，并诱导了心肌细胞肥大、核畸形、线粒体退化和间质纤维化。H2 气体吸入显著抑制了间歇低氧引起的这些变化。特别是，在复氧时或整个实验期间吸入 H2 气体在预防血脂异常和抑制 LV 心肌中超氧化物的产生方面是有效的。这些结果表明，吸入 H2 气体可有效减少与睡眠呼吸暂停相关的间歇低氧引起的氧化应激和预防 LV 重构。
