布地奈德对呼吸道合胞病毒诱发幼龄小鼠肺炎性损伤的保护作用

Protective effect of budesonide on pneumonia injury induced by respiratory syncytial virus in young mice

目的探究布地奈德对呼吸道合胞病毒(respiratory syncytial virus,RSV)诱发幼龄小鼠肺炎性损伤的作用。方法72只BABL/c幼龄小鼠随机分为健康对照组、RSV组、低剂量组、中剂量组、高剂量组以及阳性对照组,每组12只。健康对照组鼻腔滴注50μl生理盐水,其余5组给予RSV-long株病毒用于建模。健康对照组和RSV组雾化吸入等量生理盐水,低、中以及高剂量组雾化吸入0.2、0.8以及1.5 mg/kg布地奈德混悬液,阳性对照组雾化吸入46 mg/kg利巴韦林,一日1次,持续7 d。比较小鼠肺指数、肺湿/干重比(wet/dry,W/D)、肺功能以及RSV载量;流式细胞术检测Treg/辅助性T细胞(help T cell,Th17);酶联免疫吸附试验测定白介素(interleukin,IL)-17、IL-21以及IL-22水平;蛋白质印迹法检测核因子(nuclear factor,NF)κB蛋白。结果与健康对照组相比,RSV组肺指数、W/D、RSV载量、呼气峰值流速(peak exhalation flow,PEF)、吸气阻力(resistance inspiratory,RI)、呼气阻力(resistance exhalation,RE)、Th17比例、肺组织和血清IL-17、IL-21、IL-22、NF-κB蛋白增加,动态肺顺应性(dynamic lung compliance,Cdyn)、Treg以及Treg/Th17比例降低(P<0.05);与RSV组相比,低、中、高剂量组及阳性对照组肺指数、W/D、RSV载量、PEF、RI、RE以及Th17比例、肺组织、血清IL-17、IL-21、IL-22以及NF-κB蛋白降低,Cydn、Treg以及Treg/Th17比例增加(P<0.05)。结论布地奈德可通过调节NF-κB容量减轻RSV诱发幼龄小鼠肺炎性损伤,改善Treg/Th17比例。

Objective To investigate the effect of budesonide on pneumonia injury induced by respiratory syncytial virus(RSV)in young mice.Methods Seventy-two BABL/c young mice were randomly divided into healthy control group,RSV group,low dose group,medium dose group,high dose group and positive control group,with 12 mice in each group.The healthy control group was given 50μl physiological saline nasal drip,and the other 5 groups were given RSV long virus for modeling.The healthy control group and RSV group were atomized with the same amount of physiological saline,the low,medium and high dose groups were atomized with 0.2,0.8 and 1.5 mg/kg budesonide suspension,and the positive control group was atomized with 46 mg/kg ribavirin once a day for 7 days.The pulmonary index,lung wet/dry weight ratio(W/D),lung function and RSV load were compared.Treg/helper T cells(Th17)were detected by flow cytometry.The levels of interleukin(IL)-17,IL-21 and IL-22 were measured by enzyme-linked immunosorbent assay.The nuclear factor(NF)-κB protein was detected by western blotting.Results Compared with healthy control group,pulmonary index,W/D,RSV load,peak exhalation flow(PEF),resistance inspiratory(RI),resistance exhalation(RE),Th17 proportion,lung tissue and serum IL-17,IL-21,IL-22,NF-κB protein in RSV group increased,dynamic lung compliance(Cdyn),Treg,Treg/Th17 proportion were significantly decreased(P<0.05).Compared with RSV group,pulmonary index,W/D,RSV load,PEF,RI,RE,Th17 proportion,lung tissue and serum IL-17,IL-21,IL-22 and NF-κB protein were decreased in low,medium and high dose groups and positive control group,while Cdyn,Treg and Treg/Th17 proportion were increased(P<0.05).Conclusion Budesonide can reduce pneumonia injury induced by RSV and improve Treg/Th17 ratio in young mice by regulating NF-κB capacity.