Expression Of Hypoxia-inducible Factor-1β In The Lung Of Rats With Hypoxic Pulmonary Hypertension

Objectives to study expression of hypoxia-inducible factor- lp(HIF-lp) subunit in the lung of hypoxic rats and to explore the role of HIF-1 in the pathogenesis of hypoxic pulmonary hypertension.Methods twenty Wistar rats were randomly divided into control group and hypoxia group (n=20,respectively) The rat model of hypoxic pulmonary hypertension was established by exposure to hypoxia for 4 weeks according to our laboratory protocol. Digoxin-labelled cRNA probe for HIF- 1 p was prepared by in vitro transcription .Northern blot was performed by using the HIF-lp cRNA probe and In situ hybridization was also conducted with rat lung tissue sections. Results (1) The histopathology of rat lung stained with hematoxylin and eosin revealed that the thickness of pulmonary artery walls was significantly increased and the arterial lumenswere narrowed in hypoxia group ,compared to control group .(2)the results of Northern blot hybridization analysis with DIG-labelled fflF-lp cRNA probe and total RNA extracted from rat lung tissue were minimally positive in control group,but strongly positive in hypoxia group. (3)In situ hybridization analysis with hypoxic rat lung tissue revealed that HIF-lp 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.In contrast,there was no expression of HIF-lp mRNA in control rat lung.Conclusion Present data suggested that chronic hypoxia could induce pulmonary hypertension characterized by pulmonary vascular remodeling .HIF-1 mRNA expression were elevated in the lung of rat under hypoxic condition. HIF-1 may be involved in the pathophysiological changes in response to hypoxia and play important role in the development of hypoxic pulmonary hypertension.