低氧诱导因子-1β在低氧性肺动脉高压大鼠肺内表达的研究

Expression of hypoxia-inducible factor-1β in the lungs of rats with hypoxic pulmonary hypertension

目的 观察低氧诱导因子 1 β(HIF 1 β)在低氧性肺动脉高压大鼠肺内的表达 ,探讨HIF 1在低氧性肺动脉高压发病机制中的作用。方法 建立低氧性肺动脉高压大鼠模型 ,采用地高辛标记的HIF 1 βcRNA探针进行大鼠肺组织的Northern杂交和原位杂交。 结果 低氧 4周后大鼠肺动脉压增高 ,肺血管壁增厚 ,右心室重量增加。Northern杂交和原位杂交显示 :对照组肺组织偶见微弱HIF βmRNA表达 ,低氧组HIF βmRNA强阳性 ,其主要部位为支气管上皮细胞 (强阳性 )、支气管周围增生淋巴组织 (弱阳性 )和肺泡壁细胞 (弱阳性 ) ,肺动脉上皮细胞和平滑肌细胞未见阳性反应。结论 慢性低氧可导致肺动脉高压和肺血管重建 ;HIF 1 β在低氧性肺动脉高压大鼠肺内高水平表达 。

Objective To study expression of hypoxia inducible factor 1β (HIF 1β) in the lungs of hypoxic rats and to explore the role of HIF 1β in the pathogenesis of hypoxic pulmonary hypertension Methods Twenty Wistar rats were randomly divided into control group and hypoxia group The models of hypoxic pulmonary hypertension were established by exposure to hypoxia for 4 weeks according to our laboratory protocol Digoxin labelled cRNA probe for HIF 1β was prepared by in vitro transcription Northern blot was performed by using the HIF 1β cRNA probe and In situ hybridization was also conducted with rat lung tissue sections Results Northern blot hybridization showed minimally positive in the lung tissue of control group ,but strongly positive in hypoxia group In situ hybridization analysis with hypoxic rat lung tissue revealed that HIF 1β mRNA was expressed in bronchial epithelial cells (strongly positive reaction) and peribronchial proliferative lymphomatic tissue (weakly positive reaction),casually in alveolar wall cells (weakly positive reaction),but not in pulmonary arterial endothelium and smooth muscle cells Conclusions Our data suggested that chronic hypoxia could induce pulmonary hypertension characterized by pulmonary vascular remodeling HIF 1β mRNA expression was elevated in the lungs of rat under hypoxic condition HIF 1 may be involved in the pathophysiological changes in response to hypoxia and play an important role in the development of hypoxic pulmonary hypertension