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间歇低氧合并肺气肿大鼠系统与内皮炎症状态及外周血内皮祖细胞水平研究

王彦1,曹洁1,杨庆婵2,冯靖1,陈宝元1   

  1. 1. 天津医科大学总医院
    2. 天津医科大学研究生院
  • 收稿日期:2014-01-20 修回日期:2014-01-22 出版日期:2014-05-15 发布日期:2014-05-15
  • 通讯作者: 冯靖

Systematic and Endothelial Inflammation Status in Intermittent Hypoxia and Emphysema Rat Model and Level of Endothelial Progenitor Cells in Peripheral Blood

  • Received:2014-01-20 Revised:2014-01-22 Published:2014-05-15 Online:2014-05-15

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摘要： 目的 建立间歇低氧（IH）合并肺气肿重叠综合症（OS）大鼠模型，探讨OS大鼠系统及血管内皮炎症状态并观察外周血内皮祖细胞（EPC）水平的变化。 方法 自制熏箱对大鼠进行16周的熏烟暴露造成大鼠肺气肿，从13周开始，在熏烟暴露同时，通过程控产生预制的间歇低氧/再氧合（IH/ROX）环境对大鼠进行IH暴露4周。60只雄性Wistar大鼠随机分为正常组（A组）、IH组（B组）、肺气肿组（C组）和OS组（D组），暴露结束后分别以ELISA法测定血浆及右颈总动脉内皮细胞中肿瘤坏死因子（TNF）-α、白介素（IL）-6水平，Real-time-PCR法检测血管内皮细胞中RhoA mRNA含量，病理标本中测定颈动脉内中膜厚度（IMT）在全层所占比例（C-IMT%），流式细胞仪测定循环血中EPC数量。 结果 D组血浆和血管内皮细胞中TNF-α、IL-6水平以及血管内皮细胞中RhoA mRNA水平、C-IMT%均高于A、B、C组，而EPC数量均低于其它三组（均P < 0.05）。 结论 OS大鼠较单纯IH或单纯肺气肿大鼠系统及内皮损伤更加严重，同时内皮修复能力损伤也更严重，因而增加了心血管疾病风险。

关键词: 间歇低氧, 肺气肿, 内皮祖细胞, 肿瘤坏死因子-α, 白介素-6, RhoA, 颈动脉内中膜厚度

Abstract: Objective To establish the rat overlap syndrome (OS) model of intermittent hypoxia (IH) and emphysema, explore systematic and endothelial inflammation status, and observe the change of endothelial progenitor cell (EPC) level. Methods Overlap exposure was IH exposure on the base of pre-existing emphysema which was caused by 16 weeks of smoke exposure. 60 male Wistar rats were randomly divided to four groups with 15 per group according to the exposure conditions as follows: normal oxygen control group (A); IH group (B); emphysema group (C); OS group (D). After exposure, ELISA method was used to detect values of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 in plasma and in the endothelium of right common carotid artery. Real-time-PCR assay was used to analyze RhoA mRNA level in the endothelium of right common carotid artery. Flow cytometry was used to detect EPC level. We also obtained tissue of right carotid artery for counting the percentage of intima-media thickness (IMT) in the all wall (C-IMT%). Results D group had highest values of TNF-α, IL-6, RhoA mRNA and C-IMT% among all groups. The quantity of EPC were highest in D group among all groups (all P < 0.05). Conclusion OS rats had more serious vascular endothelial injury than emphysema or IH rats. Meanwhile, the repair capacity of EPC for endothelium was the worst, which increase the risk of cardiovascular diseases.

Key words: intermittent hypoxia, emphysema, endothelial progenitor cell, TNF-α, IL-6, RhoA, intima-media thickness