Gegen Qinlian Decoction Downregulates the TLR7 Signalling Pathway to Control Influenza A Virus Infection
Gegen Qinlian Decoction Downregulates the TLR7 Signalling Pathway to Control Influenza A Virus Infection
复制标题
葛根芩连汤下调TLR7信号通路控制甲型流感病毒感染
DOI：
10.1016/j.biopha.2019.109471
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发表时间：
2020-01-01
影响因子：
7.5
通讯作者：
Chen, Xiaoyin
中科院分区：
文献类型：
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作者：
Shi, Yucong;Xu, Huachong;Chen, Xiaoyin
人种药理学相关性：近年来，葛根芩连汤被应用于治疗流感病毒感染，其临床疗效已得到证实。然而，GQD作用于甲型流感病毒（IAV）的潜在机制尚未完全阐明。众所周知，传统中药（TCM）配方具有多个目标和效果。本研究从流感免疫机制的角度探讨了中药治疗流感的作用机制。本研究的目的：探讨GQD对流感病毒FM 1株感染小鼠的影响。材料与方法：将48只C57 BL/6小鼠随机分为4组：正常对照（NG）组、IAV感染（VG）组、IAV +奥司他韦（30.44 mg/kg）治疗（VO）组和IAV + GQD（9.74 g/kg）治疗（VQ）组。我们还以相同的方式将48只Toll样受体7敲除（TLR 7（-/-））小鼠分组。通过RT-qPCR测量TLR 7、髓样分化因子88（MyD 88）和核因子（NF）-κ B p65的肺mRNA表达，并且通过蛋白质印迹测量TLR 7、MyD 88和NF-κ B p65的肺蛋白质表达。结果：IAV感染后，小鼠体重下降，病毒载量增加;与NG组相比，VG组TLR 7、MyD 88和NF-κ B B p65 mRNA表达水平上调（P < 0.05）。VO组和VQ组TLR 7、MyD 88和NF-κ B B p65的mRNA和蛋白表达水平均低于VG组（P < 0.05）。IAV感染后，VG组Th 1/Th 2和Th 17/Treg细胞比例增加。VO组和VQ组Th 2和Th 1细胞数均明显增加，Th 1/Th 2比值明显低于VG组。GQD还影响CD 4（+）T细胞的分化，从而对流感病毒感染发挥保护性全身作用。总之，GQD激活了宿主的平衡炎症反应，以限制免疫病理损伤并改善临床和生存结局。
Ethnopharmacological relevance: In recent years, Gegen Qinlian decoction (GQD) has been applied to treat influenza virus infection, and its clinical effectiveness has been shown. However, the potential mechanism by which GQD acts on influenza A virus (IAV) has not been fully elucidated. Traditional Chinese medicine (TCM) formulas are well known to have multiple targets and effects. Our previous experiments examined the mechanism by which TCM can be used to treat influenza from the perspective of the influenza immune mechanism.Aim of the study: To explore the possible mechanism by which GQD affects mice infected with the FM1 strain of influenza virus.Materials and Methods: Forty-eight C57BL/6 mice were divided randomly into four groups: a normal control (NG) group, an IAV infection (VG) group, an IAV + oseltamivir (30.44 mg/kg) treatment (VO) group, and an IAV + GQD (9.74 g/kg) treatment (VQ) group. We also grouped forty-eight Toll-like receptor 7 knockout (TLR7(-/-)) mice in the same manner. The pulmonary mRNA expression of TLR7, myeloid differentiation factor 88 (MyD88), and nuclear factor (NF)-kappa B p65 was measured by RT-qPCR, and the pulmonary protein expression of TLR7, MyD88, and NF-kappa B p65 was measured by western blot. The proportions of T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cells were measured by flow cytometry.Results: IAV infection led to low body weights and high viral load. Compared with those in the NG group, the mRNA expression levels of TLR7, MyD88, and NF-kappa B p65 in the VG group were upregulated (P < 0.05). However, the mRNA and protein expression levels of TLR7, MyD88, and NF-kappa B p65 were lower in the VO and VQ groups than in the VG group (P < 0.05). IAV infection led to increased proportions of Th1/Th2 and Th17/Treg cells in the VG group. In the VO and VQ groups, both Th2 and Th1 cell numbers were increased, resulting in a lower Th1/Th2 proportion than that in the VG group.Conclusions: GQD downregulated the expression of some key TLR signalling pathway factors. GQD also affected the differentiation of CD4(+) T cells, thereby exerting a protective systemic effect on influenza virus infection. In conclusion, GQD activated a balanced inflammatory response in the host to limit immune pathological injury and improve clinical and survival outcomes.