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联合抗氧化剂对间歇低氧诱导小鼠胰腺损伤保护作用的研究

李光1,李昶1,侯刚2,康健2   

  1. 1. 葫芦岛市中心医院呼吸科
    2. 中国医科大学附属第一医院呼吸科
  • 收稿日期:2013-05-11 修回日期:2013-09-06 出版日期:2014-02-15 发布日期:2014-02-15
  • 通讯作者: 李光

Study on the protective effect of cotreatment with antioxidants against IH–Induced pancreatic injury in mice

  • Received:2013-05-11 Revised:2013-09-06 Published:2014-02-15 Online:2014-02-15

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摘要： 【摘要】 目的 探讨抗氧化剂氮氧化物4-羟基-2,2,6,6-四甲基哌啶 (tempol)和还原型谷胱甘肽(GSH)对间歇低氧（IH）小鼠胰腺损伤的保护作用。方法 雄性C57BL/6J小鼠50只按随机数字表法随机分成正常对照组（CON）、IH 2周组（IH2w）、IH+tempol 2周组(IH+Tempol)、IH+GSH 2周组(IH+GSH)、IH+tempol+GSH 2周组(IH+Tempol+GSH)，每组各10只。成功制备动物模型后，测定各组小鼠胰岛素抵抗水平，胰腺组织中丙二醛（MDA）、超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GSH)的含量，及胰腺β细胞的凋亡。结果 IH组较CON组胰岛素抵抗水平显著增加(P<0.01)， IH+Tempol+GSH组较IH组显著降低 (P<0.01)；IH组较CON组胰腺组织中MDA水平显著增加，SOD和GSH水平显著降低(P<0.01)，IH+Tempol+GSH组较IH组MDA水平显著降低、SOD及GSH水平明显增加(P<0.01)；IH组较CON组胰腺β细胞凋亡率显著增加 (P<0.01)，IH+Tempol+GSH组较IH组显著降低(P<0.01)；上述各种指标在IH+Tempol、IH+GSH组与IH组之间无显著差异(P>0.05)。结论 联合抗氧化剂tempol+GSH对IH所致小鼠胰腺损伤具有明显的保护作用，而单独应用抗氧化剂tempol或GSH对IH所致胰腺损伤无明显的保护作用。

关键词: 间歇低氧, 氧化应激, 胰岛素抵抗, 凋亡

Abstract: [Abstract] Objective To explore the protective effect of cotreatment with antioxidants 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol) and reduced glutathione (GSH) in pancreatic injury induced by IH in mice.Methods 50 male C57BL/6J mouse were equally randomly divided into control group(CON),two-week IH group(IH2w), IH+tempol+GSH group(IH+Tempol+GSH),IH+tempol group(IH+Tempol), IH+GSH group(IH+GSH).After successfully making animal model, insulin resistance level, pancreatic malondialdehyde (MDA) levels、superoxide dismutase (SOD) activity、glutathione (GSH) concentrations, and pancreaticβ-cell apoptosis were measured in all groups.Results The levels of insulin resistance were more significantly increased in IH group than those in CON group (P<0.01),but more significantly decreased in IH+Tempol+GSH group than those in IH group (P<0.01); MDA content was significantly higher (P<0.01) in the IH group than that in the CON group, but SOD activity (P<0.01) and GSH content (P< 0.01) were obviously decreased ,and MDA level was significantly lower (P<0.01) in the IH+Tempol+GSH group than that in the IH group,but SOD and GSH levels were obviously increased(P<0.01);percent of βcell apoptosis was obviously increased in IH group than that in the CON group(P<0.01), but they was significantly lower in IH+Tempol+GSH group than that in IH group(P<0.01);and there was no significantly difference in all above indexes between IH+Tempol,IH+GSH and IH groups (P>0.05). Conclusion Cotreatment with the antioxidant tempol and GSH can obviously protect IH–induced pancreatic injury in mice,however, tempol or GSH alone can not significantly inhibit this injury.

Key words: intermittent hypoxia, oxidative stress, insulin resistance, apoptosis