Department of Pediatrics, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-0366, USA.
Am J Respir Crit Care Med. 2011 Jun 1;183(11):1550-60. doi: 10.1164/rccm.201010-1755OC. Epub 2011 Mar 4.
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, for which no specific treatment or vaccine is currently available. We have previously shown that RSV induces reactive oxygen species in cultured cells and oxidative injury in the lungs of experimentally infected mice. The mechanism(s) of RSV-induced oxidative stress in vivo is not known.
To measure changes of lung antioxidant enzymes expression/activity and activation of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates detoxifying and antioxidant enzyme gene expression, in mice and in infants with naturally acquired RSV infection.
Superoxide dismutase 1 (SOD 1), SOD 2, SOD 3, catalase, glutathione peroxidase, and glutathione S-transferase, as well as Nrf2 expression, were measured in murine bronchoalveolar lavage, cell extracts of conductive airways, and/or in human nasopharyngeal secretions by Western blot and two-dimensional gel electrophoresis. Antioxidant enzyme activity and markers of oxidative cell injury were measured in either murine bronchoalveolar lavage or nasopharyngeal secretions by colorimetric/immunoassays.
RSV infection induced a significant decrease in the expression and/or activity of SOD, catalase, glutathione S-transferase, and glutathione peroxidase in murine lungs and in the airways of children with severe bronchiolitis. Markers of oxidative damage correlated with severity of clinical illness in RSV-infected infants. Nrf2 expression was also significantly reduced in the lungs of viral-infected mice.
RSV infection induces significant down-regulation of the airway antioxidant system in vivo, likely resulting in lung oxidative damage. Modulation of oxidative stress may pave the way toward important advances in the therapeutic approach of RSV-induced acute lung disease.
呼吸道合胞病毒（RSV）是导致儿童下呼吸道感染的主要原因，目前尚无特效治疗或疫苗。我们之前的研究表明 RSV 可诱导培养细胞产生活性氧（ROS），并导致实验性感染小鼠肺部氧化损伤。RSV 诱导体内氧化应激的机制尚不清楚。
测量 RSV 感染自然发生的小鼠和婴儿肺部抗氧化酶表达/活性变化，以及核因子 E2 相关因子 2（Nrf2）的激活情况，Nrf2 是一种调节解毒和抗氧化酶基因表达的转录因子。
采用 Western blot 和二维凝胶电泳法测量小鼠支气管肺泡灌洗液、传导气道细胞提取物中的超氧化物歧化酶 1（SOD1）、SOD2、SOD3、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽 S-转移酶，以及 Nrf2 表达。通过比色/免疫测定法测量小鼠支气管肺泡灌洗液或鼻咽分泌物中的抗氧化酶活性和氧化细胞损伤标志物。
RSV 感染导致小鼠肺部和重症毛细支气管炎儿童气道中 SOD、过氧化氢酶、谷胱甘肽 S-转移酶和谷胱甘肽过氧化物酶的表达和/或活性显著降低。氧化损伤标志物与 RSV 感染婴儿的临床疾病严重程度相关。病毒感染小鼠的 Nrf2 表达也明显降低。
RSV 感染可导致体内气道抗氧化系统显著下调，可能导致肺部氧化损伤。氧化应激的调节可能为 RSV 诱导的急性肺疾病的治疗方法开辟重要途径。
