Bowers Rebecca, Cool Carlyne, Murphy Robert C, Tuder Rubin M, Hopken Matthew W, Flores Sonia C, Voelkel Norbert F
Pulmonary Hypertension Center, University of Colorado Health Sciences Center, National Jewish Medical and Research Center, Denver 80262, USA.
Am J Respir Crit Care Med. 2004 Mar 15;169(6):764-9. doi: 10.1164/rccm.200301-147OC. Epub 2003 Dec 30.
Severe pulmonary hypertension (PH) occurs in a primary or "unexplained" form and in a group of secondary forms associated with a number of diseases. Because the lung tissue from patients with severe PH demonstrates complex vascular lesions, which contain inflammatory cells, we wondered whether the lung tissue from patients with severe PH was "under oxidative stress." We used immunohistochemistry to localize nitrotyrosine and 8-hydroxy guanosine in the lung tissue sections from patients with primary and secondary PH. In some lung tissue extracts, the eicosanoid metabolites 5-oxo-eicosatetraenoic acid, leukotriene B4 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 15-HETE were measured using mass spectroscopy, and superoxide dismutase amount and activity were measured. Nitrotyrosine expression was ubiquitous in all PH lungs, and 5-oxo-eicosatetraenoic acid and HETE levels were elevated in the lungs of patients with severe PH but not in those lungs that were from the patients with severe PH treated chronically with prostacyclin. We conclude that indeed the lungs from patients with severe PH are under oxidative stress and that chronic prostacyclin infusion has an antiinflammatory effect on the lung tissue.
重度肺动脉高压（PH）以原发性或“不明原因”形式出现，并存在于一组与多种疾病相关的继发性形式中。由于重度PH患者的肺组织显示出复杂的血管病变，其中含有炎症细胞，我们想知道重度PH患者的肺组织是否“处于氧化应激状态”。我们使用免疫组织化学方法在原发性和继发性PH患者的肺组织切片中定位硝基酪氨酸和8-羟基鸟苷。在一些肺组织提取物中，使用质谱法测量类花生酸代谢产物5-氧代-二十碳四烯酸、白三烯B4、5-羟基二十碳四烯酸（HETE）、12-HETE和15-HETE，并测量超氧化物歧化酶的含量和活性。硝基酪氨酸表达在所有PH肺组织中普遍存在，重度PH患者肺组织中5-氧代-二十碳四烯酸和HETE水平升高，但接受前列环素长期治疗的重度PH患者的肺组织中则未升高。我们得出结论，重度PH患者的肺组织确实处于氧化应激状态，并且长期输注前列环素对肺组织具有抗炎作用。
