呼吸道合胞病毒感染对卵白蛋白诱导哮喘小鼠气道高反应性的影响

目的观察呼吸道合胞病毒（RSV）感染对卵白蛋白（OVA）诱导的哮喘小鼠气道高反应性动态变化的影响。方法将60只BALB/c小鼠按不同时相随机分成10组,每组6只,分别为：磷酸盐缓冲液（PBS）对照组（A组）,OVA组[按测定气道反应性时点（实验第21、25、29、33 d）不同,分为B1、B2、B3、B4组],OVA/RSV组（按上述相同时点分为C1、C2、C3、C4组）,以及地塞米松处理组（D组）。采用OVA腹腔注射致敏、结合OVA持续雾化吸入及RSV滴鼻激发的方法复制哮喘动物模型。动物体描箱法测定呼气相肺阻力（RL）和胸肺动态顺应性（CTL）在不同时点的动态变化。HE染色及过碘酸雪夫（PAS）染色观察小鼠气道炎症及气道上皮杯状细胞增生变化。结果当乙酰胆碱（Ach）激发浓度大于5 g/L时,C1组RL显著高于B1组,而CTL明显低于B1组（P均〈0.05）,并且上述效应较B1组（OVA激发后2 d）明显延长,分别延长到OVA激发后6 d（C2组）、10 d（C3组）。D组RL显著低于,而CTL明显高于C1组（P均〈0.05）,气道炎症亦较C1组明显减轻。结论 OVA致敏条件下RSV感染可显著增加气道阻力,降低胸肺动态顺应性,且恢复时间较单纯OVA致敏小鼠明显延长（分别延长6 d,10 d）。提示OVA致敏条件下RSV感染导致气道病变加重,且小气道病变可能是气道高反应性增高、持续时间延长的关键因素。

Effects of Respiratory Syncytial Virus Infection on Dynamic Changes of Airway Hyperresponsiveness in Ovalhumin-Induced Asthma in Mice

Objective To investigate the effects of respiratory syncytial virus（RSV） infection on the dynamic changes of airway hyperresponsiveness（AHR） in ovalbumin（OVA）-induced asthma in mice.Methods 60 BALB/c female mice were randomly divided into PBS control group（A group,n=6）,OVA group,OVA/RSV group,dexamethasone group（D group,n=6）.Kinetics of AHR of OVA group mice was carried out on day 21,25,29 and 33（B1,B2,B3,B4 groups,n=6）,and the same with the OVA/RSV group（C1,C2,C3,C4 groups,n=6）.The mouse asthma model was established by OVA-sensitization of intraperitoneal injection and repeated inhalation of OVA while the mice in OVA/RSV group were treated with combined intranasal inoculation with RSV（1.0×106 pfu/mL in 50 μL）.Airway resistance of expiring phase（RL） and compliance of throax and lung（CTL） with different doses of acetylcholine（Ach） were measured.Lung tissue sections were stained with hematoxylin and eosin（HE） and periodic acid-Schiff（PAS） for general morphology.Results Compared with B1 group,RL increased and CTL decreased in C1 group when Ach dose is above 5 g/L（P0.05,respectively）,and the effects prolonged（6 d,10 d after challenge with OVA,respectively） much more than B1 group（2 d after challenge with OVA）.Compared with C1 group,RL decreased and CTL increased in D group and the infiltration of inflammatory cells was obviously alleviated in C1 group after treatment with dexamethasone.Conclusions Airway hyperresponsiveness increases obviously in OVA-sensitized and RSV-infected mice.The prolonged increase in RL and decrease in CTL（6 d,10 d,respectively）may imply that RSV infection aggravates airway inflammation.The small airway inflammation may play a critical role in the persistence of airway hyperresponsiveness.