Li Jianguo, Savransky Vladimir, Nanayakkara Ashika, Smith Philip L, O'Donnell Christopher P, Polotsky Vsevolod Y
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
J Appl Physiol (1985). 2007 Feb;102(2):557-63. doi: 10.1152/japplphysiol.01081.2006. Epub 2006 Nov 2.
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and associated with dysregulation of lipid metabolisms and atherosclerosis. Causal relationships between OSA and metabolic abnormalities have not been established because of confounding effects of underlying obesity. The goal of the study was to determine if CIH causes lipid peroxidation and dyslipidemia in the absence of obesity and whether the degrees of dyslipidemia and lipid peroxidation depend on the severity of hypoxia. Lean C57BL/6J mice were exposed to CIH for 4 wk with a fractional inspired O2 (FI(O2)) nadir of either 10% (moderate CIH) or 5% (severe CIH). Mice exposed to severe CIH exhibited significant increases in fasting serum levels of total cholesterol (129 +/- 2.9 vs. 113 +/- 2.8 mg/dl in control mice, P < 0.05) and low-density lipoprotein cholesterol (85.7 +/- 8.9 vs. 56.4 +/- 9.7 mg/dl, P < 0.05) in conjunction with a 1.5- to 2-fold increase in lipoprotein secretion, and upregulation of hepatic stearoyl coenzyme A desaturase 1 (SCD-1). Severe CIH also markedly increased lipid peroxidation in the liver (malondialdehyde levels of 94.4 +/- 5.4 vs. 57.4 +/- 5.2 nmol/mg in control mice, P < 0.001). In contrast, moderate CIH did not induce hyperlipidemia or change in hepatic SCD-1 levels but did cause lipid peroxidation in the liver at a reduced level relative to severe CIH. In conclusion, CIH leads to hypercholesterolemia and lipid peroxidation in the absence of obesity, and the degree of metabolic dysregulation is dependent on the severity of the hypoxic stimulus.
阻塞性睡眠呼吸暂停（OSA）的特征是慢性间歇性缺氧（CIH），并与脂质代谢失调和动脉粥样硬化有关。由于潜在肥胖的混杂效应，OSA与代谢异常之间的因果关系尚未确立。本研究的目的是确定在无肥胖情况下CIH是否会导致脂质过氧化和血脂异常，以及血脂异常和脂质过氧化的程度是否取决于缺氧的严重程度。将瘦的C57BL/6J小鼠暴露于CIH 4周，吸入氧分数（FI（O2））最低点分别为10%（中度CIH）或5%（重度CIH）。暴露于重度CIH的小鼠空腹血清总胆固醇水平显著升高（对照组小鼠为113±2.8mg/dl，重度CIH组为129±2.9mg/dl，P<0.05），低密度脂蛋白胆固醇水平显著升高（对照组为56.4±9.7mg/dl，重度CIH组为85.7±8.9mg/dl，P<0.05），同时脂蛋白分泌增加1.5至2倍，肝脏硬脂酰辅酶A去饱和酶1（SCD-1）上调。重度CIH还显著增加了肝脏中的脂质过氧化（丙二醛水平在对照组小鼠中为57.4±5.2nmol/mg，重度CIH组为94.4±5.4nmol/mg，P<0.001）。相比之下，中度CIH未诱导高脂血症或肝脏SCD-1水平变化，但相对于重度CIH确实导致肝脏脂质过氧化水平降低。总之，在无肥胖情况下CIH会导致高胆固醇血症和脂质过氧化，代谢失调的程度取决于缺氧刺激的严重程度。
