Ono S, Voelkel N F
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Lung. 1992;170(1):31-40. doi: 10.1007/BF00164753.
We recently reported that platelet-activating factor (PAF) levels increased in lung tissue after 1 subcutaneous injection of monocrotaline (MCT) (which causes lung injury), and, further, that treatment with PAF antagonists reduced pulmonary hypertension in this chronic lung injury rat model [15]. In the present study, we examined the effect of WEB 2170, a specific PAF antagonist, on MCT-induced pulmonary vascular remodeling. At 3 weeks after MCT injection, pulmonary hypertension in the animals was associated with an increase in the vessel wall thickness of the muscular arteries, reduction in number of peripheral arterioles, and right ventricular hypertrophy. In WEB 2170-treated rats, these changes were significantly less severe when compared with those observed in MCT-treated rats. In MCT-treated rats, there were significant increases in in vitro [3H]thymidine incorporation and accumulation of hydroxyproline in the lung tissue, and these changes were inhibited by WEB 2170 treatment. Our results suggest that PAF or a PAF-dependent sequence of events is involved in MCT-induced lung vascular remodeling.
我们最近报道，单次皮下注射野百合碱（MCT，可导致肺损伤）后，肺组织中的血小板活化因子（PAF）水平升高，此外，在这种慢性肺损伤大鼠模型中，用PAF拮抗剂治疗可降低肺动脉高压[15]。在本研究中，我们研究了特异性PAF拮抗剂WEB 2170对MCT诱导的肺血管重塑的影响。MCT注射后3周，动物的肺动脉高压与肌性动脉血管壁厚度增加、外周小动脉数量减少以及右心室肥厚有关。与MCT治疗的大鼠相比，接受WEB 2170治疗的大鼠的这些变化明显较轻。在MCT治疗的大鼠中，肺组织中体外[3H]胸腺嘧啶核苷掺入和羟脯氨酸积累显著增加，而这些变化被WEB 2170治疗所抑制。我们的结果表明，PAF或PAF依赖性事件序列参与了MCT诱导的肺血管重塑。
