Ono S, Tanita T, Ashino Y, Noda M, Tabata S, Hoshikawa Y, Ueda S, Nishimura T, Fujimura S
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1994 May;32(5):441-5.
Monocrotaline (MCT) causes chronic pulmonary hypertension associated with pulmonary vascular thickening in rats. Since components of the pulmonary vascular thickening are reflected in increased DNA synthesis in medial smooth muscle cells, and since platelet-activating factor (PAF) has been reported to contribute to the pulmonary hypertension induced by MCT, we examined the effect of WEB 2170, a specific PAF receptor blocker, on MCT-induced pulmonary vascular thickening and in vitro 3H-thymidine incorporation into lung tissue, as an index of stimulation of cell proliferation. In MCT-treated rats, pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular thickening developed at 3 weeks after injection. Also, in MCT-treated rat lung tissue, there was a significant increase in the in vitro 3H-thymidine incorporation rate. In WEB 2170-treated MCT rats, these changes were significantly less severe than those observed in rats receiving MCT alone. We conclude that PAF plays a role in the inflammatory process that contributes to the development of pulmonary hypertension and vascular remodeling associated with increased lung cell proliferation in MCT-treated rats.
野百合碱（MCT）可导致大鼠慢性肺动脉高压并伴有肺血管增厚。由于肺血管增厚的成分表现为中膜平滑肌细胞DNA合成增加，且据报道血小板活化因子（PAF）促成了MCT诱导的肺动脉高压，因此我们研究了特异性PAF受体阻滞剂WEB 2170对MCT诱导的肺血管增厚以及体外3H-胸腺嘧啶核苷掺入肺组织（作为细胞增殖刺激指标）的影响。在接受MCT治疗的大鼠中，注射后3周出现肺动脉高压、右心室肥大和肺血管增厚。此外，在接受MCT治疗的大鼠肺组织中，体外3H-胸腺嘧啶核苷掺入率显著增加。在接受WEB 2170治疗的MCT大鼠中，这些变化明显不如仅接受MCT的大鼠严重。我们得出结论，PAF在炎症过程中起作用，该炎症过程促成了MCT治疗大鼠中与肺细胞增殖增加相关的肺动脉高压和血管重塑的发展。
