香烟烟雾暴露对大鼠肺组织缺氧诱导因子1α表达的影响  

Effect of smoke exposure on expressional level of hypoxia inducible factor-la in the lungtissue of rats

作　　者：王红云[1] 杜永成[2] 张焕萍[3] 许建英[3] 李毅[2] 

机构地区：[1]山西医科大学,太原030001 [2]山西省人民医院呼吸科,太原030001 [3]山西医科大学第一附属医院呼吸科,太原030001

出　　处：《国际呼吸杂志》2012年第9期693-697,F0003,共6页International Journal of Respiration

基　　金：山西省基础研究项目（2008011081-2）

摘　　要：目的研究烟雾暴露对大鼠肺组织缺氧诱导因子1α（hypoxiainducible factor-1α，HIF-1α）和核因子KB（nuclear factor-1α，NF—κB）p65表达的影响，探讨烟雾暴露致大鼠肺动脉高压的发生机制。方法雄性Wistar大鼠32只，随机分为对照组、烟雾暴露4、8、12周组，每组8只，制备各组烟雾暴露模型。右心导管法测肺动脉平均压（mPAP），并计算右心肥厚指数（RVHI），荧光定量PCR测各组大鼠肺组织HIF-1α mRNA，免疫组织化学方法测各组大鼠肺组织HIF-1α、NF-κBp65蛋白表达。结果①大鼠mPAP烟雾暴露8周组[（14．700±1．125）mmHg]、12周组[（17．830±2．437）mmHg]明显高于对照组[（10．670±1．125）mmHg]，差异有统计学意义（P〈0．05）；烟雾暴露12周组大鼠RVHI（0．260±0．006）高于对照组（0．220±0．020），差异有统计学意义（P〈0．05）；②大鼠肺组织中HIF-1α mRNA相对表达量在烟雾暴露8周组（1．170±0．211）、12周组（1．360±0．185）高于4周组（0．920±0．141）及对照组（0．760±0．137），差异有统计学意义（P〈0．05）；③各烟雾暴露组大鼠肺血管平滑肌中HIF-1α及NF—κBp65蛋白的表达明显高于对照组，差异有统计学意义（P〈0．05）；④HIF-1α蛋白的表达与mPAP、RVHI、HIF-1α mRNA的相对表达量及NF-κBp65蛋白的表达均呈正相关（r=0．688、r=0．497、r=0．706、r=0．583，P值均〈0．01）。结论HIF-1α和NF—κB在烟雾暴露大鼠肺组织中表达均增高，HIF-1α和NF-κB在烟雾暴露引起肺动脉平均压增高的过程中可能发挥了一定作用。Objective To study the mechanisms of pulmonary hypertension caused by smoke exposure in researching the effect of smoke exposure on the expressional levels of hypoxia inducible factor-1α （HIF-1α） and nuclear factor-roB （NF-κB） p65 in rats lungs. Methods 32 male Wistar rats were divided randomly into control group, smoke exposure 4,8,12 weeks group. The rat models of all groups were established by smoke exposue. The mean pulmonary arterial pressure （mPAP） was measured by right- heat catheterization., and right ventricle hypertrophy index （RVHI） was measured. The relative expression of HIF-1α mRNA was detect by fluorescence quantitative PCR and HIF-1α,NF-κB p65 protein in rat lungs were detected by immunohistochemistry in all rats of four groups. Results （1） The mRAP of rats of smoke exposure 8 and 12 weeks groups were significantly higher than those of the control group （ P〈0.05） ,and the right ventricular hypertrophy was found after 8 weeks of smoke exposure,the RVHI in smoke exposure 12 weeks group was significantly higher than those others （ P 〈0.05）. （2）The relative expression of HIF-1α mRNA of rats in smoke exposure 8 and 12 weeks groups were significantly higher than those of smoke exposure 4 weeks and the control group （all P 〈0.05）. （3） The expression of HIF-1α protein in the pulmonary vascellum smooth muscle and NF-κB p65 protein were significantly higher than those of the control group （all P 〈0.05）.（4） The expressions of HIF-1α protein were positively correlated with mPAP,RVHI,the relative expression of HIF-1α mRNA and NF-κBp65 protein. Conclusions Smoke exposure increase the expession level of HIF-1α and the NF-κB, HIF-1α has an important play on pathogenesis of pulmonary hypertension caused by smoke exposure.

关 键 词：烟雾暴露 高血压 肺性 缺氧诱导因子1Α 核因子ΚB 

分 类 号：R363[医药卫生—病理学]