Gene Transfer Of Vascular Endothelial Growth Factor Attenuates Bleomycin-Induced Pulmonary Hypertension In Immature Rabbits

Objective To investigate the evolution of pulmonary hypertension, the pathological changes of pulmonary arteries, and the expression of VEGFmRNA and eNOSmRNA of pulmonary arterial endothelial cells in immature rabbits treated with intratracheal blomycin (BLM).Methods Immature rabbits (One month old ) were divided into control group (treated with intratracheal 0.2 ml/kg normal saline) and BLM group (treated with intratracheal 4u/kg BLM). Two weeks (control group 8, BLM group 10) and four weeks (control group 6, BLM group 9) after intratracheal normal saline or BLM, the systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter, the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE and in situ hybridization.Results (1) The PASP, PADP and MPAP were elevated after 2wks and 4 wks of intratracheal BLM. The PASP was 16.5 ± 2.9 mmHg and 25.2 ± 7.0 mmHg, the PADP was 8.8 ± 4.2 mmHg and 13.1 ±3.8 mmHg, the MPAP was 12.1±4.0 mmHg and 18.4±4.7 mmHg in 2wks control group and BLM group respectively(all P<0.05). The PASP was 16.7 ± 2.3 mmHg and 23.8 ± 7.1 mmHg, the PADP was 7.3 ± 1.5 mmHg and 13.8 ± 6.6 mmHg, the MPAP was 11.3±1.9 mmHg and 17.6 ± 6.3 mmHg in 4wks control group and BLM group respectively (all P<0.05) . There was no difference between 2wks and 4wks BLM group. (2) The thickness of wall increased and the cavity became narrow, and the Thickness Index (TI) and Area Index (AI) increased in middle and small pulmonary arteries after 2wks and 4 wks of intratracheal BLM. The TI was 0.52±0.16 and 0.65 ±0.16, the AI was 0.74±0.17 and 0.84±0.14 in 2wks control group and BLM group respectively (all P<0.05)The TI was 0.52±0.11and 0.64±0.15, the AI was 0.71±0.15 and 0.85 ± 0.10 in 4wks control group and BLM group respectively (all P<0.05) . There was no difference between 2wks and 4wks BLM group. (3) The level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased after 2wks and 4 wks of intratracheal BLM. The VEGFmRNA was 0.83 ± 0.09 and 0.45 ± 0.11, the eNOSmRNA was 0.79 ± 0.12 and 0.45 ± 0.12 in 2wks control group and BLM group respectively (all P<0.05). The VEGFmRNA was 0.81±0.19 and 0.46±0.15, the eNOSmRNA was 0.89± 0.14 and 0.44 ± 0.12 in 4wks control group and BLM group respectively (all P<0.05) . There was no difference between 2wks and 4wks BLM group.Conclusion The pulmonary artery pressure was elevated, the thickness of wall increased and the cavity became narrow in middle and small pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbits after 2wks and 4 wks of intratracheal 4u/kg BLM.