Schermuly Ralph Theo, Yilmaz Hüseyin, Ghofrani Hossein Ardeschir, Woyda Kathrin, Pullamsetti Soni, Schulz Andreas, Gessler Tobias, Dumitrascu Rio, Weissmann Norbert, Grimminger Friedrich, Seeger Werner
Department of Internal Medicine, Justus Liebig Universität Giessen, Germany.
Am J Respir Crit Care Med. 2005 Aug 1;172(3):358-63. doi: 10.1164/rccm.200502-296OC. Epub 2005 May 5.
Inhaled iloprost is an effective therapy for pulmonary arterial hypertension (PAH). However, no study to date has addressed the effects of inhaled iloprost on changes to pulmonary vascular structure that occur in PAH.
The present study was designed to investigate chronic antiremodeling effects of inhaled iloprost in monocrotaline (MCT)-induced PAH in rats.
Four weeks after a single injection of MCT, after full establishment of PAH, rats were nebulized with iloprost at a dose of 6 microg . kg(-1) . day(-1), or underwent sham nebulization with saline.
After 2 weeks of inhalation therapy, right ventricular pressure and pulmonary vascular resistance were reversed in rats treated with iloprost, but not in sham-treated control animals. Systemic arterial pressure was unaffected. In addition, right heart hypertrophy, the degree of pulmonary artery muscularization, and the medial wall thickness of intraacinar pulmonary arteries regressed in response to iloprost. Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed.
We conclude that the inhalation of iloprost reverses PAH and vascular structural remodeling in MCT-treated rats. This regimen suggests the possibility of an antiremodeling therapy in PAH.
吸入性伊洛前列素是治疗肺动脉高压（PAH）的有效疗法。然而，迄今为止尚无研究探讨吸入性伊洛前列素对PAH中肺血管结构变化的影响。
本研究旨在调查吸入性伊洛前列素对大鼠野百合碱（MCT）诱导的PAH的慢性抗重塑作用。
单次注射MCT四周后，在PAH完全形成后，用剂量为6微克·千克-1·天-1的伊洛前列素对大鼠进行雾化，或用盐水进行假雾化。
吸入治疗2周后，伊洛前列素治疗的大鼠右心室压力和肺血管阻力得到逆转，但假治疗的对照动物未出现这种情况。体循环动脉压未受影响。此外，右心肥大、肺动脉肌化程度和腺泡内肺动脉中膜厚度因伊洛前列素而减轻。此外，MCT诱导的基质金属蛋白酶-2和-9活性及腱生蛋白-C表达增加受到抑制。
我们得出结论，吸入伊洛前列素可逆转MCT处理大鼠的PAH和血管结构重塑。该方案提示了PAH抗重塑治疗的可能性。
