Fu Cuiping, Jiang Liyan, Zhu Fen, Liu Zilong, Li Wenjing, Jiang Hong, Ye Hongying, Kushida Clete A, Li Shanqun
Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
Sleep Breath. 2015 Dec;19(4):1467-73. doi: 10.1007/s11325-015-1144-8. Epub 2015 Feb 28.
The aim of this study was to determine whether chronic intermittent hypoxia (CIH) could affect the secretion of adipokines, such as resistin, leptin, and adiponectin, in non-obese rats and to investigate the potential mechanisms.
An established rodent model of CIH was utilized, in which rats were exposed to varying oxygen levels (7-21 %) respectively over a period of 5 weeks. The area under the curve (AUCG) and the insulin resistance index (homeostasis model of assessment for insulin resistance index, HOMA-IR) were calculated. The levels of several secretory factors in the blood were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression in adipose tissues was measured by reverse transcription-polymerase chain reaction (RT-PCR).
Glucose tolerance and the levels of adiponectin in non-obese rats were decreased in the CIH group both in the serum and adipose tissue compared with the controls, while the insulin resistance index and the levels of resistin and leptin were increased. Moreover, the expressions of hypoxia inducible factor-1α and lactate dehydrogenase A were significantly higher in chronic intermittent hypoxia rats than in control rats, suggesting the presence of adipose tissue hypoxia.
These results show that CIH leads to insulin resistance (IR) and impaired glucose tolerance (IGT) in a non-obese rodent model of obstructive sleep apnea-hypopnea syndrome, and these effects may be due to the dysregulation of adiponectin, resistin, and leptin.
本研究旨在确定慢性间歇性低氧（CIH）是否会影响非肥胖大鼠体内抵抗素、瘦素和脂联素等脂肪因子的分泌，并探究其潜在机制。
采用已建立的CIH啮齿动物模型，让大鼠在5周内分别暴露于不同氧水平（7%-21%）下。计算曲线下面积（AUCG）和胰岛素抵抗指数（胰岛素抵抗稳态模型评估指数，HOMA-IR）。通过酶联免疫吸附测定（ELISA）法检测血液中几种分泌因子的水平。采用逆转录-聚合酶链反应（RT-PCR）法检测脂肪组织中的mRNA水平和蛋白表达。
与对照组相比，CIH组非肥胖大鼠的糖耐量以及血清和脂肪组织中脂联素水平均降低，而胰岛素抵抗指数以及抵抗素和瘦素水平升高。此外，慢性间歇性低氧大鼠中缺氧诱导因子-1α和乳酸脱氢酶A的表达明显高于对照大鼠，提示存在脂肪组织缺氧。
这些结果表明，在阻塞性睡眠呼吸暂停低通气综合征的非肥胖啮齿动物模型中，CIH导致胰岛素抵抗（IR）和糖耐量受损（IGT），这些影响可能归因于脂联素、抵抗素和瘦素的失调。
