TLRs/NF-κB/P65信号通路在肾阳虚外感病证中的作用及麻黄细辛附子汤干预机制研究

流感病毒易感高危人群的防治一直是现代医学亟待解决难题，此人群所患流感多属于中医肾阳虚外感病证。我们根据大量研究证据推测，肾阳虚外感是因机体自身免疫力低下并被流感病毒传染，导致TLRs／NF-κB/P65途径发挥先天抗病毒免疫反应通路失控及产生大量炎性因子而造成病理损伤与修复之间的平衡被破坏。本课题依据前期已建立的成熟方法（苯甲酸雌二醇腹腔注射，鼻腔接种甲型流感病毒FM1）病证结合，复制肾阳虚外感小鼠模型。以此为工具，从细胞因子、蛋白激酶表达的源头TLRs／NF-κB/P65通路入手，观察经方"麻黄细辛附子汤"（MXF）对其一些重要环节TLR3、TLR7、NF-κB及其中间环节MyD88、TRIF和下游细胞因子TNF-α、INF-β及蛋白翻译控制P65/P50的作用；深入研究该通路在肾阳虚外感病证发病关键环节及MXF干预作用靶点；为深入了解该病证发病的分子机制并进行有效药物干预提供科学依据。

The prevention and treatment of influenza in high risk population which susceptible to influenza virus is always some problems crying out for solutions of modern medicine，and this kind of syndrome belongs to exogenous fever with kidney-yang deficiency according to traditional Chinese medicine. It is estimated on the basis of lots of research evidence that exogenous fever combined with kidney-yang deficiency is a kind of viral infection in the condition of immunodeficiency resulting in TLRs／NF-κB/P65 signal pathway losing their normal control in the innate immune system, lots of inflammatory factors being produced and the balance between pathological damage and repair being broken. Mice model of exogenous fever combined with deficiency of kidney-yang has been established by the our research group through benzoic acid estradiol intraperitoneal injection combined with nasal vaccination influenza viruses FM1. Using the above model, effect of Mahuang-Fuzi-Xixin decoction extraction (MFX) on TLR3, TLR7, NF-κB, MyD88, TRIF, downstream cytokines TNF-α and INF-β and P65/P50 protein translation will be studied through up-stream of cytokine expression and protein kinase expression, TLRs／NF-κB/P65 signal pathway. Key link to the onset of exogenous fever combined with kidney-yang deficiency and intervention target of MXF with this signal pathway will be investigated further in this project. It will be of profound interest to elucidate the molecular mechanism of this syndrome and provide evidence for the effective pharmacological intervention on the disease.