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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基金
国家自然科学基金(81170010,81470208)。