College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, China.
Biomed Pharmacother. 2020 Jan;121:109471. doi: 10.1016/j.biopha.2019.109471. Epub 2019 Nov 7.
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.
To explore the possible mechanism by which GQD affects mice infected with the FM1 strain of influenza virus.
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)-κB p65 was measured by RT-qPCR, and the pulmonary protein expression of TLR7, MyD88, and NF-κB 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.
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-κB p65 in the VG group were upregulated (P < 0.05). However, the mRNA and protein expression levels of TLR7, MyD88, and NF-κB 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.
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.
近年来，葛根芩连汤（GQD）已被用于治疗流感病毒感染，并已显示出其临床疗效。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，中药（TCM）方剂有多个靶点和作用。我们之前的实验从流感免疫机制的角度研究了用 TCM 治疗流感的机制。
探讨葛根芩连汤（GQD）影响 FM1 株流感病毒感染小鼠的可能机制。
将 48 只 C57BL/6 小鼠随机分为四组：正常对照组（NG）、IAV 感染组（VG）、IAV+奥司他韦（30.44mg/kg）治疗组（VO）和 IAV+GQD（9.74g/kg）治疗组（VQ）。我们还以同样的方式将 48 只 Toll 样受体 7 敲除（TLR7）小鼠分组。通过 RT-qPCR 测量 TLR7、髓样分化因子 88（MyD88）和核因子（NF）-κB p65 的肺 mRNA 表达，通过 Western blot 测量 TLR7、MyD88 和 NF-κB p65 的肺蛋白表达。通过流式细胞术测量 T 辅助（Th）1、Th2、Th17 和调节性 T（Treg）细胞的比例。
IAV 感染导致体重降低和病毒载量升高。与 NG 组相比，VG 组 TLR7、MyD88 和 NF-κB p65 的 mRNA 表达上调（P<0.05）。然而，与 VG 组相比，VO 和 VQ 组 TLR7、MyD88 和 NF-κB p65 的 mRNA 和蛋白表达水平降低（P<0.05）。IAV 感染导致 VG 组 Th1/Th2 和 Th17/Treg 细胞比例增加。在 VO 和 VQ 组中，Th2 和 Th1 细胞数量均增加，导致 Th1/Th2 比例低于 VG 组。
GQD 下调了一些关键 TLR 信号通路因子的表达。GQD 还影响 CD4 T 细胞的分化，从而对流感病毒感染产生保护全身作用。总之，GQD 激活了宿主的平衡炎症反应，限制了免疫病理损伤，改善了临床和生存结局。
