慢性间歇性缺氧条件下大鼠胰岛功能与mTOR通路相关蛋白表达的变化
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南京医科大学第一附属医院创新团队基金(IRT-16),教育部留学回国人员科研启动基金(20101174)


Changes of rat islet function and mammalian target of rapamycin pathway related protein expression under chronic intermittent hypoxia
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    摘要:

    目的:探讨慢性间歇性低氧(chronic intermittent hypoxia,CIH)条件下哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)及相关通路激活对大鼠胰岛β细胞增殖的影响及可能机制-方法:24只成年雄性SD大鼠按随机数字法平均分为两组-CIH组通过低氧舱造模,低氧条件(60 S/N2,60 S/空气,交替充入,保证舱内氧气浓度在5%~21%之间波动,每天8:30~16:30,共35 d)-酶联免疫法检测两组血糖-血清胰岛素水平并计算胰岛素抵抗指数(HOMA-IR)和β细胞胰岛素分泌功能(HOMA-β)-口服葡萄糖法检测两组大鼠糖耐量,免疫荧光法检测胰岛β细胞增殖情况,免疫印迹法检测胰腺组织mTOR及通路相关蛋白指标表达-结果:与对照组相比,CIH组大鼠空腹血糖-血清胰岛素水平及胰岛素抵抗指数升高(P < 0.01);葡萄糖耐量-胰岛β细胞功能降低(P < 0.05);ki67染色阳性的β细胞约增加了5倍;胰腺组织mTOR通路相关蛋白激活-结论:CIH条件下大鼠发生胰岛素抵抗-葡萄糖耐量降低-胰岛β细胞功能下降,而mTOR相关通路的激活可能在胰岛β细胞增殖中发挥作用-

    Abstract:

    Objective:To investigate the effect and possible mechanism of mammalian target of rapamycin (mTOR) protein and its related pathway on islet β cell proliferation in rats with chronic intermittent hypoxia (CIH). Methods:Twenty-four adult male Sprague-Dawley (SD) rats were randomly divided into two groups (the CIH group and the control group). The CIH group was fed in low oxygen cabins (60 s/N2 and 60 s/air alternately,oxygen concentrations between 5% and 21%,between 8:30~16:30 each day) for 35 days. We detected blood glucose and serum insulin levels by ELISA and calculated the insulin resistance index (HOMA-IR) and β cell insulin secretory function (HOMA-β) of the two groups. Glucose tolerance was evaluated by oral glucose tolerance test. The proliferation of pancreatic β cells was tested by immunofluorescence assay and mTOR and related pathway protein expressions were tested by Western blotting assays. Results:The fasting blood glucose,serum insulin levels and insulin resistance index increased (P < 0.01),while glucose tolerance and pancreatic β-cell function decreased (P < 0.05),in comparison with the control group. The number of ki67 positive β cells increased about five-fold while the mTOR related pathway protein expression of pancreatic tissues was activated. Conclusion:The rats in CIH condition showed insulin resistance,glucose tolerance impairment and pancreatic β-cell dysfunction;meanwhile,the activated mTOR pathway may play an important role in pancreatic β-cell proliferation.

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裴 静,姚 蒙,焦 成,张敏娟,殷 敏,程 雷.慢性间歇性缺氧条件下大鼠胰岛功能与mTOR通路相关蛋白表达的变化[J].南京医科大学学报(自然科学版),2014,(7):915-920

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  • 收稿日期:2014-03-01
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  • 在线发布日期: 2014-07-05
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