Nishimura T, Faul J L, Berry G J, Veve I, Pearl R G, Kao P N
Division of Pulmonary and Critical Care Medicine, Department of Pathology, Stanford University Medical Center, Stanford, California 94305-5236, USA.
Am J Respir Crit Care Med. 2001 Feb;163(2):498-502. doi: 10.1164/ajrccm.163.2.2006093.
Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/kg/d, by gavage): Group PMR(5-35) from Day 5 to Day 35, Group PMR5-14 from Day 5 to Day 14, and Group PMR15-35 from Day 15 to Day 35. By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (Ppa = 41 +/- 3 mm Hg) (p < 0.001), right ventricular systolic pressures (Prv,s = 45 +/- 2 mm Hg) (p < 0.01), and right ventricle/(left ventricle plus septum) (0.55 +/- 0.05) (p = 0.028) than rats in Groups PMR5-35 (Ppa = 25 +/- 3 mm Hg, Prv,s = 32 +/- 7 mm Hg, RV/LV&S = 0.42 +/- 0.06) and PMR5-14 (Ppa = 29 +/- 4 mm Hg, Prv,s = 30 +/- 5 mm Hg, RV/LV&S = 0.43 +/- 0.07). Pulmonary arterial neointimal formation (quantified by a vascular occlusion score) was more severe in vehicle-treated rats (1.93 +/- 0.03) than in Groups PMR5-14 (1.56 +/- 0.27) and PMR(5-35) (1.57 +/- 0.1) (p < 0.01). RAD attenuates the development of MCT-induced pulmonary arterial hypertension in the pneumonectomized rat.
在给予野百合碱（MCT）4周后，肺切除大鼠会出现肺动脉高压（PH）和肺血管新内膜形成。雄性Sprague-Dawley大鼠在左肺切除术后第7天注射MCT（60mg/kg）。三组（n = 5）接受40-O-（2-羟乙基）-雷帕霉素（RAD，2.5mg/kg/d，经口灌胃）：PMR(5 - 35)组从第5天至第35天，PMR5 - 14组从第5天至第14天，PMR15 - 35组从第15天至第35天。到第35天时，接受赋形剂的大鼠的平均肺动脉压（Ppa = 41±3mmHg）（p < 0.001）、右心室收缩压（Prv,s = 45±2mmHg）（p < 0.01）以及右心室/（左心室加室间隔）（0.55±0.05）（p = 0.028）均高于PMR5 - 35组（Ppa = 25±3mmHg，Prv,s = 32±7mmHg，RV/LV&S = 0.42±0.06）和PMR5 - 14组（Ppa = 29±4mmHg，Prv,s = 30±5mmHg，RV/LV&S = 0.43±0.07）的大鼠。在接受赋形剂治疗的大鼠中，肺动脉新内膜形成（通过血管闭塞评分量化）（1.93±0.03）比PMR5 - 14组（1.56±0.27）和PMR(5 - 35)组（1.57±0.1）更严重（p < 0.01）。RAD可减轻肺切除大鼠中MCT诱导的肺动脉高压的发展。
