Oxidative stress in severe pulmonary hypertension

Oxidative stress in severe pulmonary hypertension
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DOI:
10.1164/rccm.200301-147oc
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发表时间:
2004-03-15
影响因子:
24.7
通讯作者:
Voelkel, NF
Voelkel, NF
中科院分区:
医学1区
文献类型:
--
作者:
Bowers, R;Cool, C;Voelkel, NF

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重度肺动脉高压(PH)以原发性或“原因不明”的形式以及与许多疾病相关的一组继发性形式发生。由于严重PH患者的肺组织显示出复杂的血管病变,其中含有炎性细胞,我们想知道严重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定位原发性和继发性PH患者肺组织切片中的硝基酪氨酸和8-羟基鸟苷。在一些肺组织提取物中,使用质谱测量类二十烷酸代谢物5-氧代-二十碳四烯酸、白三烯B-4 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量和活性。硝基酪氨酸表达普遍存在于所有PH肺,5-氧代-二十碳四烯酸和HETE水平升高,在肺严重PH患者,但不是在肺严重PH患者长期前列环素治疗。我们的结论是,严重PH患者的肺确实处于氧化应激状态,慢性前列环素输注对肺组织有不良影响。
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 B-4 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.