Li Deng, Huachong Xu, Peng Pang, Ke Zheng, Jiao Nie, Xianlin Wu, Bin Yu, Jia Chen, Xiaoyin Chen
Altern Ther Health Med. 2017 Nov;23(6):16-22.
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.
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。