慢性低氧性肺动脉高压大鼠肺内血管内皮生长因子表达的变化

Changes of the Gene Expression of Vascular EndothelialGrowth Factor in the Lung of Rats with ChronicHypoxic Pulmonary Hypertension

为了解低氧对肺内血管内皮生长因子（ＶＥＧＦ）基因表达的影响及ＶＥＧＦ在肺动脉高压发生中的作用，以常压低氧建立大鼠肺动脉高压模型，采用Ｅｌｉｓａ法检测大鼠肺动脉血血清ＶＥＧＦ的含量改变，以体外转录并用ＤＩＧ－ＵＴＰ标记的ＶＥＧＦｃＲＮＡ探针进行肺组织原位杂交，检测大鼠肺内ＶＥＧＦｍＲＮＡ表达的变化。结果发现：低氧３周后，大鼠形成明显的肺动脉高压；大鼠肺动脉血血清中ＶＥＧＦ含量在低氧３周组为４２０．３±７３．１ｐｇ／ｍｌ，明显高于对照组的３２２．２±５８．１ｐｇ／ｍｌ（Ｐ＜０．０１）；原位杂交显示，低氧大鼠肺小动脉管壁出现明显的ＶＥＧＦｍＲＮＡ表达，说明低氧在引起肺动脉高压的同时可刺激肺小动脉管壁，使ＶＥＧＦｍＲＮＡ表达增强，导致ＶＥＧＦ的合成和分泌增加，后者可能在低氧性肺动脉高压发生过程中起一定的作用。

To observe the effect of chronic hypoxia on the gene expression of vascular endothelial growth factor (VEGF) in rat′s lung, and the role of VEGF in the pathogenesis of hypoxic pulmonary hypertension, thirteen male Wistar rats were exposed to isobaric hypoxia for 3 weeks. The pulmonary artery pressure was measured by right cardiac catheterization. The serum level of VEGF was measured by Elisa. The VEGF cRNA was labeled with digoxigeninUTP by in vitro transcription. The expression of VEGF mRNA in the lung was examined by hybridization in situ. The pulmonary artery pressure was significantly increased after hypoxic exposure. The serum level of VEGF in rats treated with hypoxia (4203±731 pg/ml) was significantly increased in comparison with that of normal rats (3222±581 pg/ml). The VEGF hybridization signals on the wall of pulmonary arteriole were significantly increased in rats with pulmonary hypertension. Chronic hypoxia can markedly increase expression of VEGF mRNA in the pulmonary arteriole and hence stimulate VEGF synthesis and secretion. The increase of VEGF may play a role in the developing process of hypoxic pulmonary hypertension.