天津医药

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HIF-1α在间歇低氧合并肺气肿大鼠肝细胞凋亡中的机制研究

战京燕1,陈怀永2,吴琦2,孙昕2,冯靖3,李雪2,徐龙2,包翠萍2   

  1. 1. 天津医科大学研究生院
    2. 天津市海河医院
    3. 天津市天津医科大学附属总医院
  • 收稿日期:2013-08-29 修回日期:2013-09-10 出版日期:2014-02-15 发布日期:2014-02-15
  • 通讯作者: 吴琦

The Mechanism underlying the Role of HIF-1α during Hepatocyte Apoptosis in Intermittent Hypoxia with Pulmonary Emphysema Rats

  • Received:2013-08-29 Revised:2013-09-10 Published:2014-02-15 Online:2014-02-15

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摘要： 【摘要】 目的 探讨间歇低氧(IH)合并肺气肿对大鼠肝脏低氧诱导因子-1α（HIF-1α）、Bax、Bcl-2表达的影响，以及HIF-1α与Bax、Bcl-2的相关性，进一步探究HIF-1α在肝细胞凋亡中的作用机制。方法 将60只大鼠随机分为4组：正常对照组，正常饲养；IH组，每天9：00-17：00于低氧舱内交替通入30s氮气和90s空气，8h/d；肺气肿组，每天8:00和18:00于熏箱内熏烟，各30min；IH合并肺气肿组，每天8:00和18:00于熏箱内熏烟，各30min，并于9：00-17：00向低氧舱内交替通入30s氮气和90s空气，8h/d，暴露14周后，处死大鼠。采用荧光实时定量（qRT ）-PCR法测定肝组织中HIF-1α、Bax、Bcl-2表达水平。结果 IH合并肺气肿组HIF-1α mRNA、Bax mRNA、Bax/Bcl-2水平较正常对照组、IH组、肺气肿组升高(均P<0.05)，IH合并肺气肿组Bcl-2 mRNA水平较正常对照组、肺气肿组降低(均P<0.05)，较IH组无显著差(P>0.05)；HIF-1α与Bax、Bax/Bcl-2呈正相关(r分别为0.732、0.699)，与Bcl-2呈负相关(r=-0.705)。结论 IH合并肺气肿可诱导肝细胞HIF-1α mRNA、Bax mRNA、Bcl-2 mRNA表达上调，其上调程度较单纯IH和肺气肿大，HIF-1α与Bax、Bcl-2相关，表明HIF-1α可能通过调控凋亡基因Bax、Bcl-2的表达来参与肝细胞的凋亡。

关键词: 低氧诱导因子-1α, 间歇低氧, 肺气肿, 重叠综合征, 肝细胞, 凋亡

Abstract: [Abstract] Objective To investigate the effect of intermittent hypoxia (IH) with pulmonary emphysema on the expression of hypoxia inducible factor-1α（HIF-1α）Bax and Bcl-2, and reveal the mechanism underlying the role of HIF-1α in hepatocyte apoptosis. Methods Sixty rats were divided randomly into the four groups: the normal control group, rats were treated normally; IH group, rats were treated by 30s nitrogen and then 90s air, which was called one cycle, and rats were treated by 120 cycle from nine clock to seventeen clock daily;pulmonary emphysema group, rats were treated by smudging, the condition of smudging was set for half an hour, twice a day (eight clock and sixteen clock); IH with pulmonary emphysema group, rats were treated by 120 cycle which were composed of 30s nitrogen and then 90s air from nine clock to seventeen clock daily. After exposed fourteen weeks, the whole rats were killed. qRT-PCR assay was conducted to detect the expression of HIF-1α mRNA, Bax mRNA, Bcl-2 mRNA in live tissues. Correlation analysis was applied to reveal the relationship between HIF-1α and Bax, Bcl-2. Results The expression of HIF-1α, Bax, Bax/Bcl-2 in IH with pulmonary emphysema group was significantly higher than that in other groups (P<0.05), and the expression of Bcl-2 in IH with pulmonary emphysema group was significantly lower than the pulmonary emphysema group and the normal control group, but the expression of Bcl-2 in IH with pulmonary emphysema group did not show significant difference compared with the IH group. Positive correlations existed between HIF-α and Bax, Bax/Bcl-2, while negative correlations existed between HIF-α and Bcl-2. Conclusion The expression of HIF-1α mRNA, Bax mRNA, Bcl-2 mRNA was induced in hepatocyte under the condition of intermittent hypoxia with pulmonary emphysema, and the induction was greater than that under purely intermittent hypoxia and pulmonary emphysema. HIF-1α expression correlated with Bax and Bcl-2, suggesting that HIF-1α may promote the hepatocyte apoptosis through transcriptional coactivators, Bax and Bcl-2.

Key words: HIF-1α, intermittent hypoxia, pulmonary emphysema, overlap syndrome, hepatocyte, apoptosis