呼吸道合胞病毒感染后期Poly(I:C)诱发小鼠气道炎症及其机制研究

赵柯婷, 龙晓茹, 李伟, 谢军, 任洛, 邓昱, 谢晓虹, 臧娜, 王莉佳, 刘恩梅

中国当代儿科杂志 ›› 2016, Vol. 18 ›› Issue (5) : 455-459.

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中国当代儿科杂志 ›› 2016, Vol. 18 ›› Issue (5) : 455-459. DOI: 10.7499/j.issn.1008-8830.2016.05.015
论著·实验研究

呼吸道合胞病毒感染后期Poly(I:C)诱发小鼠气道炎症及其机制研究

  • 赵柯婷1, 龙晓茹1, 李伟1, 谢军1, 任洛1, 邓昱2, 谢晓虹2, 臧娜1, 王莉佳1, 刘恩梅2
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Airway inflammation induced by Poly(I:C) stimulation in the late stage of respiratory syncytial virus infection in mice and its mechanism

  • ZHAO Ke-Ting1, LONG Xiao-Ru1, LI Wei1, XIE Jun1, REN Luo1, DENG Yu2, XIE Xiao-Hong2, ZANG Na1, WANG Li-Jia1, LIU En-Mei2
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摘要

目的 探讨呼吸道合胞病毒(RSV)感染后再发呼吸道病毒感染时诱发气道炎症及反复喘息的致病机制。方法 64只6~8周雌性BALB/c小鼠随机分为对照组、RSV组、Poly(I:C)组及RSV+Poly(I:C)组(n=16)。收集各组肺泡灌洗液(BALF),计数BALF中细胞总数及分类计数,苏木精-伊红(HE)染色观察肺部病理损伤,检测小鼠气道反应性(AHR),ELISA法检测BALF中IFN-γ、IL-4、IL-13、基质金属蛋白酸9(MMP-9)及基质金属蛋白酶抑制物-1(TIMP-1)水平。结果 RSV+Poly(I:C)组小鼠的气道炎症细胞浸润总数及AHR较其他3组显著增高(P<0.05)。RSV+Poly(I:C)组小鼠的肺组织病理损伤较对照组及RSV组加重(P<0.01);BALF中MMP-9水平较其他3组明显升高(P<0.05),IL-4及TIMP-1显著低于RSV组(P<0.01)。结论 RSV感染后病毒再感染可能引起MMP-9/TIMP-1表达失衡,加重气道炎症反应。

Abstract

Objective To investigate the pathogenic mechanisms of airway inflammation and recurrent wheezing induced by recurrent respiratory virus infection after respiratory syncytial virus (RSV) infection. Methods Sixtyfour female BALB/c mice (aged 6-8 weeks) were randomly divided into four groups: control, RSV, Poly(I:C), and RSV+Poly(I:C) (n=16 each). The bronchoalveolar lavage fluid (BALF) was collected on the 3rd day after Poly(I:C) administration, and the total cell number and differential counts in BALF were determined. Hematoxylin-eosin staining was used to observe pulmonary pathological changes. The airway responsiveness was detected. ELISA was used to measure the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-13 (IL-13), matrix metallopeptidase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in BALF. Results Compared with the other three groups, the RSV+Poly(I:C) group had significant increases in the total number of inflammatory infiltrating cells in the airway, airway responsiveness, and MMP-9 level in BALF (P<0.05). The RSV+Poly(I:C) group showed more severe pulmonary tissue injuries compared with the control and RSV groups (P<0.01). Compared with the RSV group, the RSV+Poly(I:C) group showed significant reductions in the levels of IL-4 and TIMP-1 in BALF (P<0.01). Conclusions Viral re-infection in the late stage of RSV infection may cause an imbalance of MMP-9/TIMP-1 expression and thus contribute to aggravated airway inflammation.

关键词

呼吸道合胞病毒 / Poly(I:C) / 气道炎症 / 小鼠

Key words

Respiratory syncytial virus / Poly(I:C) / MMP-9/TIMP-1 / Airway inflammation / Mice

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赵柯婷, 龙晓茹, 李伟, 谢军, 任洛, 邓昱, 谢晓虹, 臧娜, 王莉佳, 刘恩梅. 呼吸道合胞病毒感染后期Poly(I:C)诱发小鼠气道炎症及其机制研究[J]. 中国当代儿科杂志. 2016, 18(5): 455-459 https://doi.org/10.7499/j.issn.1008-8830.2016.05.015
ZHAO Ke-Ting, LONG Xiao-Ru, LI Wei, XIE Jun, REN Luo, DENG Yu, XIE Xiao-Hong, ZANG Na, WANG Li-Jia, LIU En-Mei. Airway inflammation induced by Poly(I:C) stimulation in the late stage of respiratory syncytial virus infection in mice and its mechanism[J]. Chinese Journal of Contemporary Pediatrics. 2016, 18(5): 455-459 https://doi.org/10.7499/j.issn.1008-8830.2016.05.015

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基金

国家自然科学基金(81170010,81470208)。

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