作者：董伟然1，张燕2，安会波3，张建伟3，周亮1

单位：

1.050031河北省石家庄市，河北省儿童医院呼吸一B科　2.102206北京市，中国疾病预防控制中心病毒病预防控制所3.050031河北省石家庄市，河北省儿童医院病理科

Units：

1.Respiratory Department 1B, Children's Hospital of Hebei Province, Shijiazhuang 050031, China2.National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China3.Department of Pathology, Children's Hospital of Hebei Province, Shijiazhuang 050031, China

关键词：

呼吸道合胞病毒；布地奈德；重组人干扰素α-1b；雾化干预；白细胞介素13；CD2+ T淋巴细胞

Keywords：

Respiratory syncytial viruses; Budesonide; Recombinant human interferon α-1b; Atomizationintervention; Interleukin-13; CD2+ T lymphocytes

CLC：

　R 373.1

DOI：

10.12114/j.issn.1008-5971.2022.00.265

Funds：

2020年度河北省医学科学研究课题计划（20200220）

摘要：

目的　分析吸入用布地奈德联合重组人干扰素α-1b注射液雾化干预对呼吸道合胞病毒（RSV）感染幼鼠模型血清白介素13（IL-13）水平及CD2+ T淋巴细胞占比的影响。方法　本实验时间为2020-07-23至2020-08-02。采用随机数字表法将32只SPF级Wistar幼鼠分为空白对照组、阳性对照组、布地奈德组及联合用药组，每组8只。除空白对照组外，其余各组采用滴鼻法建立RSV感染幼鼠模型；从实验第4天开始，空白对照组和阳性对照组幼鼠给予0.9%氯化钠溶液雾化干预，布地奈德组幼鼠给予吸入用布地奈德混悬液雾化干预，联合用药组幼鼠给予吸入用布地奈德混悬液联合重组人干扰素α-1b注射液雾化干预，各组均连续雾化干预5 d。雾化干预结束后，观察各组幼鼠的一般情况，采用酶联免疫吸附试验（ELISA）双抗体夹心法检测各组幼鼠血清IL-13水平，采用流式细胞仪检测各组幼鼠血清CD2+ T淋巴细胞占比。结果　本实验过程中各组幼鼠均未出现死亡情况，其中空白对照组幼鼠毛发光滑、有光泽，呼吸频率正常，活动自如，精神状态良好，进食正常，体温正常；阳性对照组幼鼠毛发无光泽、竖立，呼吸急促、喘息，伴有发热、寒战，行动迟缓，精神萎靡或烦躁不安，厌食；布地奈德组和联合用药组幼鼠毛发光滑、有光泽，呼吸频率稍快，行动、饮食基本正常，精神状态一般。阳性对照组幼鼠血清IL-13水平、CD2+ T淋巴细胞占比高于空白对照组，布地奈德组、联合用药组幼鼠血清IL-13水平高于空白对照组（P ＜0.05）；布地奈德组、联合用药组幼鼠血清IL-13水平、CD2+ T淋巴细胞占比低于阳性对照组（P ＜0.05）；联合用药组幼鼠血清IL-13水平低于布地奈德组（P ＜0.05）。结论　吸入用布地奈德联合重组人干扰素α-1b注射液雾化干预可降低RSV感染幼鼠模型血清IL-13水平、CD2+ T淋巴细胞占比，其可能通过抑制炎症反应、调节免疫功能而提高治疗效果。

Abstract：

Objective　To investigate the effects of budesonide for inhalation combined with recombinant humaninterferon α-1b injection aerosol intervention on serum interleukin-13 (IL-13) levels and the proportion of CD2+ T lymphocytesin young mouse model of respiratory syncytial virus (RSV) infection. Methods　This experiment was conducted from 2020-07-23 to 2020-08-02. Using random number table method, 32 SPF Wistar young mice were divided into blank control group, positivecontrol group, budesonide group and combination group, with 8 young mice in each group. Except for the blank control group, theother groups were established the RSV infection model of young mouse by nasal drip method. From the 4th day of the experiment,the young mice in the blank control group and the positive control group were given 0.9% sodium chloride solution aerosolintervention, the young mice in the budesonide group were given budesonide suspension for inhalation, the young mice in thecombination group were given budesonide suspension for inhalation combined with recombinant human interferon α-1b injection,and each group received continuous nebulization intervention for 5 days. After the nebulization intervention, the general conditionsof the young mouse in each group were observed, enzyme-linked immunosorbent assay (ELISA) double-antibody sandwichmethod was used to detect serum IL-13 levels of young mouse in each group, and flow cytometry was used to detect the proportionof serum CD2+ T lymphocytes in young mouse of each group. Results　During the experiment, the young mice in each group didnot die. Among them, the young mice in the blank control group had smooth and shiny hair, normal breathing rate, free movement,good mental state, normal eating and normal body temperature; the young mice in the positive control group showed dull and erecthair, shortness of breath, wheezing, accompanied by fever, chills, slow movement, listlessness or restlessness, and anorexia; theyoung mice in the budesonide group and the combination group had smooth and shiny hair, slightly faster breathing rate, normalmovement and diet, and normal mental state. The serum IL-13 level and the proportion of CD2+ T lymphocytes of the young mousein the positive control group were higher than those in the blank control group, and the serum IL-13 level of the young mice in thebudesonide group and the combination group was higher than that in the blank control group (P < 0.05) ; the serum IL-13 leveland the proportion of CD2+ T lymphocytes of the young mouse in the budesonide group and the combination group were lower thanthose in the positive control group (P < 0.05) ; the serum IL-13 level of the young mouse in the combination group was lower thanthat in the budesonide group (P < 0.05) . Conclusion　Budesonide for inhalation combined with recombinant human interferonα-1b injection aerosol intervention can reduce the serum IL-13 level and the proportion of CD2+ T lymphocytes in the RSVinfectedyoung mouse model, inhibit the inflammatory response, regulate immune function, and improve the therapeutic effect.

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