Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma
Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma
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DOI：
10.1016/j.jaci.2009.10.065
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发表时间：
2010-03-01
影响因子：
14.2
通讯作者：
Ghosh, Balaram
中科院分区：
文献类型：
--
作者：
Mabalirajan, Ulaganathan;Ahmad, Tanveer;Ghosh, Balaram
背景：L-精氨酸代谢酶如一氧化氮合酶和精氨酸酶之间微妙平衡的紊乱可能导致L-精氨酸对内皮型一氧化氮合酶的可获得性降低，从而增加硝基氧化应激和气道高反应性。目的：本研究观察大剂量L-精氨酸对L-精氨酸代谢酶的影响以及随后的生物学效应，如环鸟苷生成、脂质过氧化、过氧亚硝酸盐、过氧亚硝酸盐和呼吸道炎症。方法：采用卵蛋白致敏和激发小鼠模型，给予不同剂量的L-精氨酸。结果：L精氨酸可显著降低AHR和包括支气管肺泡灌洗液嗜酸性粒细胞增多症、TH2细胞因子、转化生长因子-β(1)、杯状细胞化生和上皮下纤维化在内的气道炎症反应。此外，L精氨酸还能提高肺组织中eNO水平和环鸟苷一磷酸水平，降低硝基酪氨酸、8-异前列腺素和8-羟基-2‘-脱氧鸟苷等硝基氧化应激指标。结论：L精氨酸可改善过敏性气道炎症相关的一氧化氮代谢紊乱，减轻哮喘的某些症状。(《过敏与免疫杂志》2010；125：626-35。)
Background: Disturbance in the delicate balance between L-arginine metabolizing enzymes such as nitric oxide synthase (NOS) and arginase may lead to decreased L-arginine availability to constitutive forms of NOS (endothelial NOS), thereby increasing the nitro-oxidative stress and airway hyperresponsiveness (AHR).Objective: In this study, we investigated the effects of high doses of L-arginine on L-arginine metabolizing enzymes and subsequent biological effects such as cyclic guanosine monophosphate production, lipid peroxidation, peroxynitrite, AHR, and airway inflammation in a murine model of asthma.Methods: Different doses of L-arginine were administered to ovalbumin sensitized and challenged mice. Exhaled nitric oxide, AHR, airway inflammation, T(H)2 cytokines, goblet cell metaplasia, nitro-oxidative stress, and expressions of arginase 1, endothelial NOS, and inducible NOS in lung were determined.Results: L-arginine significantly reduced AHR and airway inflammation including bronchoalveolar lavage fluid eosinophilia, TH2 cytokines, TGF-beta(1), goblet cell metaplasia, and subepithelial fibrosis. Further, L-arginine increased ENO levels and cyclic guanosine monophosphate in lung and reduced the markers of nitro-oxidative stress such as nitrotyrosine, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. This was associated with reduced activity and expression of arginase 1, increased expression of endothelial NOS, and reduction of inducible NOS in bronchial epithelia.Conclusion: We conclude that L-arginine administration may improve disordered nitric oxide metabolism associated with allergic airway inflammation, and alleviates some features of asthma. (J Allergy Clin Immunol 2010;125:626-35.)