PAF antagonists inhibit monocrotaline-induced lung injury and pulmonary hypertension.
PAF antagonists inhibit monocrotaline-induced lung injury and pulmonary hypertension.
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PAF 拮抗剂可抑制野百合碱诱导的肺损伤和肺动脉高压。
DOI：
10.1152/jappl.1991.71.6.2483
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Voelkel,NF
中科院分区：
文献类型：
--
作者：
Ono,S;Voelkel,NF
皮下注射野百合碱（MCT）后1-3周，部分大鼠肺血小板活化因子（PAF）水平升高。我们测试了特异性PAF拮抗剂WEB 2086和WEB 2170对MCT诱导的肺损伤以及随后的肺动脉高压和右心室肥大的影响。在注射后3周，任何一种药物治疗均可降低MCT诱导的肺动脉高压和右心室肥大。注射后1周，WEB 2170治疗减少了MCT诱导的肺血管渗漏，而仅在早期渗漏阶段进行WEB 2086治疗也减少了3周时MCT诱导的右心室肥大。在MCT注射后第3周和第4周之间用WEB 2170治疗可抑制4周时右心室肥大的进展。这些结果表明，PAF有助于早期肺血管渗漏，这个泄漏阶段是重要的肺动脉高压和右心室肥大的发展在MCT治疗的大鼠。此外，似乎PAF作用有助于维持慢性炎症过程，该过程涉及其他脂质介质（白藜芦醇和白三烯）的合成并导致肺动脉高压。结论PAF在MCT诱导的炎性肺损伤和肺动脉高压中起一定作用。
Lung platelet-activating factor (PAF) levels increased in some rats at 1–3 wk after subcutaneous injection of monocrotaline (MCT). We tested the effect of specific PAF antagonists, WEB 2086 and WEB 2170, on MCT-induced lung injury and subsequent pulmonary hypertension and right ventricular hypertrophy. Treatment with either agent decreased MCT-induced pulmonary hypertension and right ventricular hypertrophy at 3 wk after injection. Treatment with WEB 2170 reduced MCT-induced pulmonary vascular leak at 1 wk after injection, and WEB 2086-treatment exclusively during the early leak phase also decreased MCT-induced right ventricular hypertrophy at 3 wk. Treatment with WEB 2170 between the 3rd and 4th wk after MCT injection inhibited the progression of right ventricular hypertrophy at 4 wk. These results suggest that PAF contributes to the early pulmonary vascular leak, and this leak phase is important for the development of pulmonary hypertension and right ventricular hypertrophy in MCT-treated rats. Furthermore, it appears that PAF action contributes to the maintenance of a chronic inflammatory process that involves the synthesis of other lipid mediators (prostaglandins and leukotrienes) and leads to pulmonary hypertension. We conclude that PAF has a role in the MCT-induced inflammatory lung injury and pulmonary hypertension.