间歇性低氧大鼠氧化应激状态与胰岛素抵抗的相关实验研究及吡格列酮干预作用

Related experimental study of oxidative stress and insulin resistance of chronic intermittent hypoxia rats and the intervention of pioglitazone

目的:探讨吡格列酮对间歇性低氧大鼠氧化应激与胰岛素抵抗的干预作用。方法:建立OSAHS模型,将SD雄性大鼠36只随机分为常氧对照组、模型组、吡格列酮干预组,每组12只。干预组给予吡格列酮10ml·kg-1·d-1灌胃,模型、对照组均予等量生理盐水灌胃。于实验8周终点处死大鼠,硫代巴比妥酸法、酶联免疫吸附法、比色法、蛋白免疫印迹等方法观察各组大鼠血清TNF-α、MDA、GSH-Px、HOMA-IR及胰腺组织NF-κB蛋白的表达情况。结果:与对照组比较,模型、干预组大鼠血清TNF-α、MDA、FBG、FINS、HOMA-IR及胰腺组织NF-κB蛋白表达均升高,GSH-Px水平降低(P<0.05);与模型组比较,干预组血清TNF-α、MDA、FBG、FINS、HOMA-IR及胰腺组织NF-κB蛋白表达均降低,GSH-Px水平升高(P<0.05)。结论:吡格列酮可通过抑制NF-κB核转位降低慢性间歇行低氧氧化应激水平,改善胰岛素抵抗状态。

Objective： To investigate the intervention effect of pioglitazone on the oxidative stress lev el and insulin resistance of chronic intermittent hypoxia rats. Methods： Obstructive sleep aponea- hypopnea syndrorne（OSAHS） models in rats were established. 36 male Sprague-Dawley（SD） rats were randomized into 3 groups： the normoxic control group, the model group, and the pioglitazone intervention group. Each group had 12 rats. Rats in the intervention group were gavaged with piogl- itazone （10 ml·kg-1·d-1）, and those in the model and control group were treated with isovalent normal saline by gavage. The rats were sacrificed at the end of 8 weeks and changes were detected a.bout the serum TNF-α, MDA, GSH-Px, FBG, FINS, HOMA-IR, and the expression of, pancreas tissue NF-κB protein as well by TBA test, ELISA, colorimetry and western blotting. Results： Compared with the control group, the serum TNF-a, MDA, FBG, FINS, HOMA-IR, and the ex pression of pancreas tissue NF-κB protein in the model and intervention group increased, while GSH-Px level declined（P〈0.05）; Compared with the model group, the serum TNF-a, MDA, FBG, FINS, HOMA-IR and pancreas tissue NF-κB protein expression in the intervention rats declined, while GSH-Px level rised（P〈0.05）. Conclusion： Pioglitazone can degrade the oxidative stress level and improve the insulin resistance state in chronic intermittent hypoxia rats through inhibiting the NF-κB translocation.