我国传统医学古方中曾使用人参治疗类似于今天流感重症炎症的疾病，而现代研究认为人参不适用于早期急性炎症的治疗；治疗流感常用黄芩等清热解毒的药物，一般认为黄芩直接通过抗病原微生物的活性产生作用。本研究为探讨这两种药物在流感病毒感染中的作用，建立了流感病毒感染的小鼠模型和细胞模型，从整体动物、细胞以及分子水平探讨和比较这两种药物的主要成分黄芩苷和人参皂苷在病毒感染造成的炎症反应中的作用。实验表明，流感病毒感染显著上调TLR3表达，并继而引起炎症因子的高表达，引发动物肺部及细胞的炎症损伤。病毒感染造成GR表达在细胞的抑制和组织中的升高，参与调节炎症反应的发生和感染造成的免疫抑制，并对TLR3的表达有一定的调控作用，提示GR在流感感染过程中有控制炎症与免疫反应平衡的重要作用。对细胞和动物模型的研究表明，黄芩苷与人参皂苷都没有明确的抗流感病毒作用。虽然黄芩苷与人参皂苷均通过抑制炎症反应改善动物预后，但作用方式不同。黄芩苷主要作用于GR，对TLR3和炎症因子的下调是GR通路的下游反应，人参总皂苷具有激活GR通路和降低TLR3的双重作用，Rb1则是其中直接下调TLR3高表达的主要成分。同时，对感染造成的免疫失衡，黄芩苷表现出一定的免疫抑制和复杂的调节作用，人参总皂苷和Rb1则有较强的双向免疫调节作用，提示其不同的药理作用特点。本研究为进一步认识流感感染的病理变化，尤其是TLR3和GR在其中的作用及其相互之间的关系提供了实验依据；对黄芩苷和人参皂苷作用的比较研究有助于全面了解人参和黄芩的作用机理，指导临床合理用药和新药开发。
Panax ginseng C.A. Mey has been used for the treatment of severe inflammatory symptom of influenza since the ancient China, but it was evaluated to be harmful in the early acute inflammation by modern pharmacological researches. Scutellaria baicalensis Georgi is now widely used for its antivirus activity instead. The aim of this study was to explore and compare the actions of baicalin and ginsenosides, the main components of scutellaria and ginseng in inflammation caused by influenza A virus infection, from animal, cellular and molecular levels in vitro and in vivo. Influenza virus infection could up-regulate TLR3, leading to a high-level of inflammatory factors in both in vitro and in vivo models, suggesting that TLR3 could play a key role in inflammation of influenza infection. The infection could inhibit glucocorticoid receptor (GR) expression in vitro, which is responsible to regulate inflammation. But the infection increased GR repression in vivo, which might contribute to the immune suppression. These intricate effects suggested that GR could be important to control the balance of inflammatory and immune responses in the influenza infection. Comparative researches showed that baicalin and ginsenosides could not decrease the virus number in the infected lung. Though they alleviated the pneumonia by inhibiting the inflammatory response, they relied on different mechanisms. Baicalin suppressed TLR3 and inflammatory factors by increasing GR, while ginseng total saponins (GS) could both up-regulate GR and down-regulate TLR3 directly; Rb1 might be the component to down-regulate TLR3 directly. At the same time, baicalin and ginsenosides could regulate the immune dysfunction in infection, in which baicalin mainly inhibited the response, while ginsenosides showed a better bidirectional effect, suggesting different symptoms of baicalin and ginsenosides in clinical application. The research provides an experimental basis to further comprehension of the pathological changes in influenza infection, especially the role of TLR3 and GR, as well as their relationship. The pioneer investigation helps to understand the mechanisms of ginseng and scutellaria comprehensively, give direction in clinical administration and supply references for exploitation of novel drug targets.
