间歇低氧小鼠胰岛素抵抗增加及其适应性的研究

Study on the increased insulin resistance of mice with intermittent hypoxia and its adaptability

目的探讨间歇低氧(intermittent hypoxia,IH)小鼠胰岛素抵抗增加及其适应性的机制。方法雄性C57BL/6J小鼠40只随机分成正常对照组(CON组)、持续低氧2周组(SH 2周组)、间歇低氧2周组(IH 2周组)和间歇低氧4周组(IH 4周组),每组各10只。成功复制动物模型后,测定各组小鼠胰岛素抵抗水平、氧化应激指标、Bcl-2和Bax蛋白表达及胰腺β细胞的凋亡。结果 IH 2周组较CON组胰岛素抵抗水平显著提高(30 min,P<0.05;60 min和90 min,P<0.01),氧化应激水平显著提高(P<0.01),Bax蛋白/Bcl-2蛋白比率显著增高(P<0.01),胰腺β细胞凋亡率显著增高(P<0.01);IH 4周组较IH 2周组在30 min时间点上胰岛素抵抗水平差异没有统计学意义(P>0.05),在60 min和90 min时间点上胰岛素抵抗水平降低(P<0.01),氧化应激水平显著降低(P<0.01),Bax蛋白/Bcl-2蛋白比率显著降低(P<0.01),胰腺β细胞凋亡率显著降低(P<0.01);SH 2周组与CON组上述各项指标比较差异无统计学意义(P>0.05)。结论 IH可能是胰岛素抵抗的病理生理机制之一,且胰腺对慢性IH(4周)具有适应性。

[ Objective ] To explore the mechanism of the increased insulin resistance of mice with intermittent hypoxia and its adaptability. [Methods] 40 male C57BIJ6J mouse were equally randomly divided into control group （CON group）, two-week IH group （IH 2 w group）, two-week sustained hypoxia （SH 2 w group） and four-week IH group （IH 4 w group）. After successfully making animal model, insulin resistance level, oxidative stress indexes, the expression of Bel-2 and Bax protein, and pancreatic β-cell apoptosis were measured in all groups. [ Results ] The levels of insulin resistance, the levels of oxidative stress （30 min, P〈0.05; 60 and 90 min, P〈0.01）, the rate of Bax protein/ Bcl-2 protein and percent of pancreatic 13cell apoptosis were more significantly increased in IH 2 w group than those in CON group; there is not significant different in insulin resistance level in IH 4 w group than that in IH 2 w group （30 rain, P 〉0.05）, but obviously decreased （60 and 90 min, P 〈0.01）, and the levels of oxidative stress, the rate of Bax protein/Bcl-2 protein and percent of pancreatic 13 cell apoptosis were obviously lower in the IH 4 w group than in the IH 2 w group （P 〈0.01）; there is not obvious different at every time point between CON and SH 2 w groups in all above indexes （P 〉0.05）. [ Conclusion ] IH may be one of the pathophysiological basis of insulin resistance, and pancreas can adapt to chronic IH （4 w）.