Pathophysiology of bleomycin-induced pulmonary hypertension in immature rabbits / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the evolution of pulmonary hypertension induced by intratracheal bleomycin (BLM) in immature rabbits.</p><p><b>METHODS</b>Immature rabbits were divided into control and BLM groups. Two and four weeks 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.</p><p><b>RESULTS</b>Pulmonary artery pressure was elevated 2 weeks and 4 weeks after intratracheal BLM. Two weeks after treatment PASP was (16.5 +/- 2.9 compared with 25.2 +/- 7.0) mmHg, PADP (8.8 +/- 4.2 compared with 13.1 +/- 3.8) mmHg, MPAP (12.1 +/-4.0 compared with 18.4 +/-4.7) mmHg in control and BLM groups, respectively; meanwhile 4 weeks after treatment, PASP was (16.7 +/-2.3 compared with 23.8 +/-7.1) mmHg, PADP (7.3 +/-1.5 compared with 13.8 +/-6.6) mmHg, MPAP (11.3 +/- 1.9 compared with 17.6 +/- 6.3) mmHg in control and BLM groups, respectively. The thickness of arterial wall increased and the cavity became narrow, and the thickness index (TI) and area index (AI) increased in middle and small pulmonary arteries 2 weeks and 4 weeks after intratracheal BLM. Two weeks after treatment TI was 0.52 +/- 0.16 compared with 0.65 +/- 0.16, AI 0.74+/- 0.17 compared with 0.84 +/- 0.14 in control and BLM groups, respectively; meanwhile 4 weeks after treatment TI was 0.52 +/- 0.11 compared with 0.64 +/- 0.15, AI 0.71 +/- 0.15 compared with 0.85 +/- 0.10 in control and BLM groups. The levels of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased 2 weeks and 4 weeks after intratracheal BLM. Two weeks after treatment VEGFmRNA was 0.83 +/- 0.09 compared with 0.45 +/- 0.11, eNOSmRNA 0.79 +/- 0.12 compared with 0.45 +/- 0.12 in control and BLM groups, respectively; meanwhile 4 weeks after VEGFmRNA was 0.81 +/- 0.19 compared with 0.46 +/- 0.15, eNOSmRNA 0.89 +/- 0.14 compared with 0.44 +/- 0.12 in control and BLM groups, respectively.</p><p><b>CONCLUSION</b>Intratracheal bleomycin may induce the pathological changes of pulmonary arteries and decrease the expression of VEGFmRNA and eNOSmRNA in immature rabbits, which results in pulmonary hypertension.</p>