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湿气可通过上调TLR7信号通路促进甲型流感病毒感染并恶化其预后。

Dampness Can Promote the Influenza A Virus and Worsen Its Prognosis by Upregulating the TLR7 Signaling Pathway.

作者信息

Li Deng, Huachong Xu, Peng Pang, Ke Zheng, Jiao Nie, Xianlin Wu, Bin Yu, Jia Chen, Xiaoyin Chen

出版信息

Altern Ther Health Med. 2017 Nov;23(6):16-22.

Abstract

Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung. Design • The research team performed an animal study. Setting • The study was performed at Jinan University (Guangzhou, China). Animals • A total of 144 specific-pathogen-free, C57BL/6j mice were included in the study, divided into 6 groups with 24 mice in each group. Intervention • The mice were randomly divided into the 6 groups, with 24 mice in each group: (1) group A: normal mice, a control group; (2) group B: normal mice living in a damp environment, a second control group; (3) group C: virally infected mice living in a normal environment; (4) group D: virally infected mice living in a damp environment; (5) group E: virally infected mice living in a normal environment and receiving treatment with 0.2 mL/d of 0.78 mg/mL oseltamivir; and (6) group F: virally infected mice living in a damp environment and receiving treatment with 0.2 mL/d of 0.78 mg/mL oseltamivir. Outcome Measures • Real-time quantitative polymerase chain reaction was used to measure the mRNA expression of TLR7, myeloid differentiation primary response gene 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6), interleukin 1 receptor-associated kinase 4 (IRAK4), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the TLR7 signaling pathway and the viral replication level in the lung. Results • The mice began to lose weight after being infected with IAV, especially those mice in groups D and F, where the mice were lost weight more quickly than those in groups C and E. The damages in group F were more serious than for mice in group E. In groups C and D, the mRNA TLR7, MyD88, TRAF6, IRAK4, and NF-κB were upregulated after viral infection (P < .01). After the IAV infection, the expression of TLR7, MyD88, TRAF6, and NF-κB mRNA in group D was higher (P < .01) than in group C. The oseltamivir treatment reduced the mRNA expression in the TLR7 signaling pathways (P < .01), both in the damp environment and normal environment. The expression of mRNA in the TLR7 signaling pathways was lower in group F than in group E (P < .01). Conclusions • The study suggests that dampness can promote the IAV infection and worsen its prognosis by upregulating the TLR7 signaling pathway.

摘要

背景 • 甲型流感病毒(IAV)爆发日益被视为一个全球公共卫生问题,影响着世界上很大一部分人口。多项研究提供了流行病学证据,表明潮湿和霉菌始终与多种过敏及呼吸道影响相关,但这些研究聚焦于导致过敏的与潮湿相关的病原微生物,而非潮湿本身。

目的 • 本研究旨在探讨潮湿环境对IAV传播的促进作用,并通过上调肺组织中Toll样受体7(TLR7)信号通路来确定其对IAV预后的不良影响。

设计 • 研究团队开展了一项动物研究。

地点 • 研究在暨南大学(中国广州)进行。

动物 • 本研究共纳入144只无特定病原体的C57BL/6j小鼠,分为6组,每组24只。

干预 • 小鼠被随机分为6组,每组24只:(1)A组:正常小鼠,为对照组;(2)B组:生活在潮湿环境中的正常小鼠,为第二对照组;(3)C组:生活在正常环境中的病毒感染小鼠;(4)D组:生活在潮湿环境中的病毒感染小鼠;(5)E组:生活在正常环境中且接受每日0.2 mL、浓度为0.78 mg/mL的奥司他韦治疗的病毒感染小鼠;(6)F组:生活在潮湿环境中且接受每日0.2 mL、浓度为0.78 mg/mL的奥司他韦治疗的病毒感染小鼠。

观察指标 • 采用实时定量聚合酶链反应检测TLR7信号通路中TLR7、髓样分化初级反应基因88(MyD88)、肿瘤坏死因子受体相关因子6(TRAF6)、白细胞介素1受体相关激酶4(IRAK4)以及活化B细胞核因子κB(NF-κB)的mRNA表达,以及肺组织中的病毒复制水平。

结果 • 感染IAV后小鼠开始体重减轻,尤其是D组和F组的小鼠,其体重减轻速度比C组和E组的小鼠更快。F组的损伤比E组的小鼠更严重。在C组和D组中,病毒感染后TLR7、MyD88、TRAF6、IRAK4和NF-κB的mRNA表达上调(P < 0.01)。IAV感染后,D组中TLR7、MyD88、TRAF6和NF-κB mRNA的表达高于C组(P < 0.01)。奥司他韦治疗降低了潮湿环境和正常环境中TLR7信号通路的mRNA表达(P < 0.01)。F组中TLR7信号通路的mRNA表达低于E组(P < 0.01)。

结论 • 该研究表明,潮湿可通过上调TLR7信号通路促进IAV感染并恶化其预后。

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