Morris Claudia R, Poljakovic Mirjana, Lavrisha Lisa, Machado Lorenzo, Kuypers Frans A, Morris Sidney M
Department of Emergency Medicine, Children's Hospital and Research Center at Oakland, Oakland, CA 94609, USA.
Am J Respir Crit Care Med. 2004 Jul 15;170(2):148-53. doi: 10.1164/rccm.200309-1304OC. Epub 2004 Apr 7.
Recent studies suggest that a nitric oxide (NO) deficiency and elevated arginase activity may play a role in the pathogenesis of asthma. Although much attention has been directed toward measurements of exhaled NO in asthma, no studies to date have evaluated levels of plasma arginase or arginine, the substrate for NO production, in patients with asthma. This study, therefore, measured amino acid levels, arginase activity, and nitric oxide metabolites in the blood of patients with asthma, as well as NO in exhaled breath. Although levels of virtually all amino acids were reduced, patients with asthma exhibited a striking reduction in plasma arginine levels compared with normal control subjects without asthma (45 +/- 22 vs. 94 +/- 29 microM, p < 0.0001), and serum arginase activity was elevated (1.6 +/- 0.8 vs. 0.5 +/- 0.3 micromol/ml/hour, asthma vs. control, p < 0.0001). High arginase activity in patients with asthma may contribute to low circulating arginine levels, thereby limiting arginine bioavailability and creating a NO deficiency that induces hyperreactive airways. Addressing the alterations in arginine metabolism may result in new strategies for treatment of asthma.
近期研究表明，一氧化氮（NO）缺乏和精氨酸酶活性升高可能在哮喘发病机制中起作用。尽管人们对哮喘患者呼出NO的测量给予了很多关注，但迄今为止尚无研究评估哮喘患者血浆精氨酸酶或精氨酸（NO产生的底物）的水平。因此，本研究测量了哮喘患者血液中的氨基酸水平、精氨酸酶活性和一氧化氮代谢产物，以及呼出气体中的NO。尽管几乎所有氨基酸水平均降低，但与无哮喘的正常对照受试者相比，哮喘患者血浆精氨酸水平显著降低（45±22对94±29微摩尔，p<0.0001），血清精氨酸酶活性升高（1.6±0.8对0.5±0.3微摩尔/毫升/小时，哮喘组对对照组，p<0.0001）。哮喘患者的高精氨酸酶活性可能导致循环精氨酸水平降低，从而限制精氨酸的生物利用度并造成NO缺乏，进而诱发气道高反应性。解决精氨酸代谢的改变可能会产生治疗哮喘的新策略。
