Faul J L, Nishimura T, Berry G J, Benson G V, Pearl R G, Kao P N
The Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California 94305-5236, USA.
Am J Respir Crit Care Med. 2000 Dec;162(6):2252-8. doi: 10.1164/ajrccm.162.6.2002018.
This paper reports the effect of triptolide (a diterpenoid triepoxide) on the development of monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague- Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Rats received therapy from Day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml of ethanol/cremophor intraperitoneally, every other day, n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmonary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 versus 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significantly less right ventricular hypertrophy (RVH) and pulmonary arterial neointimal formation. In a rescue experiment, rats initiated therapy on Day 21. At Day 35, vehicle-treated rats (n = 4) had higher mPAP (40 +/- 9 mm Hg), greater RVH, and more severe pulmonary arterial neointimal formation than rats that received triptolide (0.25 mg/kg every other day, n = 7, mPAP 30 +/- 4 mm Hg) and rats that received triptolide (0.2 mg/kg daily, n = 7, mPAP 25 +/- 5 mm Hg, p < 0.01). In pneumonectomized rats that receive MCT, triptolide attenuates the development of pulmonary hypertension and RVH, and promotes regression of pulmonary arterial neointimal formation.
本文报道了雷公藤甲素（一种二萜类三环氧物）对肺切除大鼠中野百合碱（MCT）诱导的肺动脉高压发展的影响。雄性Sprague-Dawley大鼠在左肺切除术后第7天注射MCT（60mg/kg）。大鼠从第5天至第35天接受雷公藤甲素治疗（0.25mg/kg腹腔注射，隔天一次，n = 10）或溶剂对照（0.1ml乙醇/聚氧乙烯蓖麻油腹腔注射，隔天一次，n = 10）。到第35天，雷公藤甲素治疗的大鼠平均肺动脉压（mPAP）低于溶剂对照治疗的大鼠（mPAP 21±3对42±5mmHg，p<0.001）。雷公藤甲素治疗的大鼠右心室肥厚（RVH）和肺动脉内膜新生也明显较少。在一项挽救实验中，大鼠在第21天开始治疗。在第35天，溶剂对照治疗的大鼠（n = 4）比接受雷公藤甲素（0.25mg/kg隔天一次，n = 7，mPAP 30±4mmHg）和接受雷公藤甲素（0.2mg/kg每天一次，n = 7，mPAP 25±5mmHg，p<0.01）的大鼠具有更高的mPAP（40±9mmHg）、更严重的RVH和更严重的肺动脉内膜新生。在接受MCT的肺切除大鼠中，雷公藤甲素可减轻肺动脉高压和RVH的发展，并促进肺动脉内膜新生的消退。
