PDF(Pubmed)
Abstract：
Influenza A virus (IAV) infection in pregnancy resembles a preeclamptic phenotype characterised by vascular dysfunction and foetal growth retardation. Given that low dose aspirin (ASA) is safe in pregnancy and is used to prevent preeclampsia, we investigated whether ASA or NO-conjugated aspirin, NCX4016, resolve vascular inflammation and function to improve offspring outcomes following IAV infection in pregnant mice. Pregnant mice were intranasally infected with a mouse adapted IAV strain (Hkx31; 104 plaque forming units) and received daily treatments with either 200µg/kg ASA or NCX4016 via oral gavage. Mice were then culled and the maternal lungs and aortas collected for qPCR analysis, and wire myography was performed on aortic rings to assess endothelial and vascular smooth muscle functionality. Pup and placentas were weighed and pup growth rates and survival assessed. IAV infected mice had an impaired endothelial dependent relaxation response to ACh in the aorta, which was prevented by ASA and NCX4016 treatment. ASA and NCX4016 treatment prevented IAV dissemination and inflammation of the aorta as well as improving the pup placental ratios in utero, survival and growth rates at post-natal day 5. Low dose ASA is safe to use during pregnancy for preeclampsia and this study demonstrates that ASA may prove a promising treatment for averting the significant vascular complications associated with influenza infection during pregnancy.
摘要：
妊娠中的甲型流感病毒（IAV）感染类似于以血管功能障碍和胎儿生长迟缓为特征的先兆子痫表型。鉴于低剂量阿司匹林（ASA）在怀孕期间是安全的，并且用于预防先兆子痫，我们调查了ASA或NO结合的阿司匹林，NCX4016，解决血管炎症和功能，以改善怀孕小鼠IAV感染后的后代结果。妊娠小鼠用小鼠适应的IAV菌株(Hkx31;104菌斑形成单位)鼻内感染,并通过口服管饲法接受每日200μg/kgASA或NCX4016治疗。然后剔除小鼠，收集母体肺和主动脉进行qPCR分析，并对主动脉环进行了线肌电图,以评估内皮和血管平滑肌的功能.称重幼犬和胎盘，并评估幼犬的生长速度和存活率。IAV感染的小鼠在主动脉中对ACh的内皮依赖性舒张反应受损，ASA和NCX4016治疗可以预防。ASA和NCX4016治疗可预防IAV播散和主动脉炎症，并改善子宫内幼仔胎盘比例，出生后第5天的存活率和生长率。低剂量ASA在妊娠期间用于先兆子痫是安全的，这项研究表明，ASA可能是避免妊娠期间与流感感染相关的重大血管并发症的有希望的治疗方法。
