Zablockienė Birutė, Kačergius Tomas, Ambrozaitis Arvydas, Žurauskas Edvardas, Bratchikov Maksim, Jurgauskienė Laimutė, Zablockis Rolandas, Gravenstein Stefan
Clinic of Infectious and Chest Diseases, Dermatovenerology and Allergology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
In Vivo. 2018 May-Jun;32(3):473-478. doi: 10.21873/invivo.11263.
BACKGROUND/AIM: Severe pulmonary influenza A virus (IAV) infection causes lung inflammation and expression of inducible nitric oxide synthase (iNOS), leading to overproduction of nitric oxide (NO). We studied whether zanamivir reduces pulmonary inflammation through inhibition of NO production in mice.
We treated IAV-infected mice daily with intranasal zanamivir. Controls were infected and either placebo-treated or untreated, or not infected and placebo-treated. Mice were weighed daily. After euthanasia on day 3, lungs were excised and bronchoalveolar lavage was performed and fluid nitrite concentration was determined. Lungs were analyzed microscopically. iNOS and IAV RNA levels in lungs were assessed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR).
Mice undergoing zanamivir treatment had less weight loss, viral replication, and lung damage, as well as significant reductions of local NO and iNOS mRNA synthesis (p<0.05).
Zanamivir is associated with an anti-inflammatory effect mediated through inhibition of NO production in IAV-infected mice.
背景/目的：严重的甲型流感病毒（IAV）感染会引发肺部炎症并诱导型一氧化氮合酶（iNOS）表达，进而导致一氧化氮（NO）过量产生。我们研究了扎那米韦是否通过抑制小鼠体内NO的产生来减轻肺部炎症。
我们每天给感染IAV的小鼠鼻腔内注射扎那米韦。对照组小鼠感染后分别接受安慰剂治疗、不接受治疗，或未感染但接受安慰剂治疗。每天对小鼠称重。在第3天实施安乐死后，取出肺部并进行支气管肺泡灌洗，测定灌洗液中亚硝酸盐浓度。对肺部进行显微镜分析。使用定量逆转录-聚合酶链反应（RT-qPCR）评估肺部iNOS和IAV RNA水平。
接受扎那米韦治疗的小鼠体重减轻较少、病毒复制减少、肺损伤减轻，同时局部NO和iNOS mRNA合成显著降低（p<0.05）。
扎那米韦在IAV感染的小鼠中具有通过抑制NO产生介导的抗炎作用。
