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肺气肿合并间歇低氧大鼠模型肝脏的氧化应激及炎症损伤

刘亚萌1,高梦丽1,曹洁2,冯靖2,陈宝元2   

  1. 1. 天津医科大学
    2. 天津医科大学总医院
  • 收稿日期:2013-06-17 修回日期:2013-09-13 出版日期:2014-02-15 发布日期:2014-02-15
  • 通讯作者: 刘亚萌

Hepatic Oxidative Stress and Inflammation in Sleep Intermittent Hypoxia and Emphysema Rat Model

  • Received:2013-06-17 Revised:2013-09-13 Published:2014-02-15 Online:2014-02-15

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摘要： 目的 建立肺气肿合并睡眠间歇低氧的大鼠模型，并在此基础上探讨该大鼠模型肝脏的氧化应激和炎症损伤。 方法 将60只雄性Wistar 大鼠均分成4组按以下条件连续暴露8周：A组（正常组）：正常饲养，不予处理；B组（肺气肿组）：常氧状态，每天熏烟2次，30min/次；C组（间歇低氧组）：每天于9:00~17:00以5%O2/平衡N230秒和空气90秒交替通气约8h/d；D组（肺气肿合并间歇低氧组）：每天熏烟2次，30min/次，于9:00~17:00以5%O2/平衡N230秒和空气90秒交替通气约8h/d。暴露结束后从各组中均随机抽取5只大鼠股动脉取血，测其血气值；采集各组剩余大鼠的肺脏染色后光镜下观察计算平均内衬间隔（MLI）、平均肺泡数（MAN）；肝脏染色后光镜观察计算肝脏炎症损伤的病理评分，测定肝脏IL-6和TNF-α的水平及SOD、CAT和MDA的水平。 结果 B和D组大鼠肺病理均呈明显肺气肿样改变；B、D组MLI均大于A、C组，B、D组MAN均低A、C组(P <0.05);B、C和D组大鼠的肝脏总的SOD及CAT的活力值均低于A组，且D组明显低于B、C组(P <0.05)，B、C和D组大鼠的肝脏的MDA的水平均高于A组，且D组明显高于B、C组( P <0.05)。B、C、D组肝脏IL-6、TNF-α的含量及肝脏炎症损伤病理评分均高于A组，且D组肝脏IL-6、TNF-α的含量及肝脏炎症损伤病理评分明显高于B、C组(P <0.05)。 结论 肺气肿和睡眠间歇低氧在引起肝脏的氧化应激和炎症损伤的进展过程中有协同作用。

关键词: 肺气肿1, 间歇低氧2, 肝脏3, 氧化应激4, 炎症5

Abstract: Objectives To develop a sleep intermittent hypoxia (SIH) and emphysema rat model and to explore whether SHE results in more severe hepatic oxidative stress and inflammation than emphysema alone or sleep intermittent hypoxia alone .Methods Sixty male Wistar rats were assigned to 4 groups with 15 per group according to the exposure conditions. Group A (control group), sham smoke exposure(smoke exposure, exposed to smoke of 15 cigarettes twice everyday, 8weeks) and sham SIH exposure (5% O2, 8hours); Group B (Emphysema group), smoke exposure and sham SIH exposure; Group C (SIH group), sham smoke exposure and SIH exposure ; Group D (Emphysema and SIH group), smoke exposure and SIH exposure . At the end of exposure, 5 rats in each group were randomly selected for arterial blood gas analysis. In the rest 10 rats in each group, We also obtained tissue blocks of liver for pathologic scoring and measurements of liver oxidative stress (measuring hepatic oxidative stress enzymes, superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) concentration)and liver inflammation (measuring hepatic inflammatory factor interleukin -6 (IL-6) protein and tumor necrosis factor a (TNF-a) protein).Results Characteristics of emphysema were obvious in group B and D.Group B and D had higher mean linear intercept (MLI) values than group A and C (all P <0.05). group B and D had lower mean alveolar number (MAN) values than group A and C. MAN values in group D were the lowest (all P <0.05).SOD and CAT values were lower and MDA values were higher in group B, C and D than group A(all P <0.05)). SOD and CAT values were the lowest in group D ,MDA values were the highest in group D (all P <0.05); Histological scores of liver , IL-6 and TNF-α values were higher in group B, C and D than group A , group D were the highest (all P <0.05) .Conclusions Emphysema and SIH have synergistic action in causing of hepatic oxidative stress and inflammation.

Key words: emphysema1, intermittent hypoxemia2, liver3, oxidative stress4, inflammation5