Antioxidant treatment ameliorates respiratory syncytial virus-induced disease and lung inflammation
Antioxidant treatment ameliorates respiratory syncytial virus-induced disease and lung inflammation
复制标题
抗氧化剂治疗可改善呼吸道合胞病毒引发的疾病和肺部炎症
DOI：
10.1164/rccm.200603-319oc
复制
发表时间：
2006-12-15
影响因子：
24.7
通讯作者：
Casola, Antonella
中科院分区：
文献类型：
--
作者：
Castro, Shawn Monique;Guerrero-Plata, Antonieta;Casola, Antonella
理论基础：呼吸道合胞病毒(RSV)是儿童下呼吸道感染的主要原因。没有任何治疗方法能显著改善这种感染患者的临床结果。最近的证据表明，氧化应激在急、慢性肺炎性疾病的发病机制中起重要作用。目的：研究抗氧化剂对呼吸道合胞病毒(RSV)所致肺部炎症、临床疾病和呼吸道高反应性(AHR)的影响。方法：BALB/c小鼠感染101个RSV空斑形成单位的RSV，同时给予或不给予抗氧化剂丁基羟基苯甲醚(BHA)。采用量热法测定支气管肺泡灌洗液(BAL)中丙二醛和4-羟基壬烯醛的含量。用Bio-Plex法检测细胞因子和趋化因子，用酶联免疫吸附试验检测白三烯。结果：BHA治疗可明显减轻RSV感染小鼠肺组织的氧化应激反应，表现为降低RSV感染小鼠肺组织中丙二醛和4-羟基壬烯醛的含量。BHA治疗还能减少RSV引起的临床疾病和体重减轻，抑制中性粒细胞向肺内募集，并显著减少RSV感染后肺细胞因子和趋化因子的产生。同样，抗氧化剂治疗可减轻RSV诱导的AHR。结论：氧化应激的调节代表了一种潜在的新的药理学方法，可以改善RSV诱导的急性肺炎症，并有可能预防与RSV感染相关的长期后果，如支气管哮喘。
Rationale: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in children. No treatment has been shown to significantly improve the clinical outcome of patients with this infection. Recent evidence suggests that oxidative stress could play an important role in the pathogenesis of acute and chronic lung inflammatory diseases. We do not known whether RSV induces pulmonary oxidative stress and whether antioxidant treatment can modulate RSV-induced lung disease.Objectives: To investigate the effect of antioxidant administration on RSV-induced lung inflammation, clinical disease, and airway hyperreactivity (AHR).Methods: BALB/c mice were infected with 101 plaque-forming units of RSV, in the presence or absence of orally administered butylated hydroxyanisole (BHA), an antioxidant. Malondialdehyde and 4-hydroxynonenal were measured in bronchoalveoar lavage (BAL) by calorimetric assay. Cytokines and chemokines were measured in BAIL by Bio-Plex and leukotrienes were measured by enzyme-linked immunosorbent assay. AHR to methacholine challenge was measured by whole-body plethysmography.Results: BHA treatment significantly attenuated RSV-induced lung oxidative stress, as indicated by the decrease of malondialdehyde and 4-hydroxynonenal content in BAIL of RSV-infected mice. RSV-induced clinical illness and body weight loss were also reduced by BHA treatment, which inhibited neutrophil recruitment to the lung and significantly reduced pulmonary cytokine and chemokine production after RSV infection. Similarly, antioxidant treatment attenuated RSV-induced AHR.Conclusion: Modulation of oxidative stress represents a potential novel pharmacologic approach to ameliorate RSV-induced acute lung inflammation and potentially prevent long-term consequences associated with RSV infection, such as bronchial asthma.