The Experimental Study On Intervention Of YangfeiHuoxue Decoction To The Immune And Inflammatory Response Of PBMCs In Pulmonary Fibrosis According To The TCM Theory Of "Dry Win"

Pulmonary Fibrosis(PF)is one refractory diseases of the most respiratory diseases,its characteristic pathological is chronic interstitial inflammation.PF includes three pathological process:the diffuse alveolar inflammation,the alveolar disorders structure and pulmonary fibrosis stage,and it is a chronic underlying disease.For the complex etiology,unknown pathological mechanism,slow and sustained disease processes,and finally lead to respiratory failure and deatht due to the irreversible lung tissue fibrosis pathological results,PF now is a outcome for variety of common pathological lung injury diseases.Therefore,delaying the development of the lung injury to pulmonary fibrosis,predicting outcome,timely truncation of the procress,reversing the disease may be the important sense to prevention and control of pulmonary fibrosis.According to the theory of physiological characteristics and the common pathological changes of lung in TCM,the process of pulmonary fibrosis along with the body fluid loss,metabolic disorder,compromised with " inner dry" theory,and is closely related to clinical visible series of Qi deficiency,Yin deficiency,Blood deficiency,Blood stasis,and the conditions of the related zang-fu organs.Therefore,keep its main pathogenesis,nourishing Yin and replenishing Qi and at the same time invigorateing the circulation of blood,are the important way to treat pulmonary fibrosis in traditional Chinese medicine method.Its representative decoction named "YangfeiHuoxue Decoction".Through the system combing traditional Chinese and western literature,inductive analysis "dry win" theory,this study replicates the animal models of pulmonary fibrosis in rats,mainly researches on rat peripheral blood mononuclear cells,in order to observe how the decoction influence the PBMCs immune inflammation of pulmonary fibrosis,among this,the inflammatory factors and Notch signaling pathway are the mainly research object,discusses the raising lung qi and the mechanism of action of dry method for prevention and treatment of pulmonary fibrosis.This paper is divided into three parts:Part one:literature research.This part systematically combs the latest literature from two aspects of TCM and western medicine.Firstly,mainly summarize the role of individual nuclear cells in peripheral blood in pulmonary fibrosis and the related contents of various signaling pathways,especially the Notch signaling pathway.PBMCs is an important part of the immune inflammatory response process.They participate in the early inflammatory response of lung injury,release inflammatory factors and protect the immune function of the body.In the late,PBMCs is involved in escape process of immune monitoring,excessive activation of the immune response,the release of immune molecules,to evade immune surveillance,thus escape the immune clearance,in this process,macrophages,lymphocytes,dendritic cells(DC)the immune cells conduct the antigen presenting function,promote the expression of immune molecules and inflammation factors,activate more immune cells or converted into mature antigen presenting cells,achieve the goal of escape immune surveillance in the role of signal transduction of passage.In the process of pulmonary fibrosis,EMT(Epithelial mesenchymal transformation)and the process of fiber cells proliferation,to some extent is also escape immune surveillance,so pulmonary fibrosis with dormant and long-term evolution process with the stimulation of inflammation and immune activation.There is increasing evidence that the Notch signaling pathway plays a vital role in the balance of multiple organ development,tumor disease and homeostasis,especially the lung and its immune system.Secondly,in terms traditional Chinese and western medicine treatment of pulmonary fibrosis,there have numerous literature,this article summarizes the new understanding of TCM for pulmonary fibrosis as a basis for the induction,and in recent years the clinical experience of TCM and combination of traditional Chinese and western medicine treatment of pulmonary fibrosis.Part two:theoretical research.In the case of "the theory of Yin and Yang":"Over forty,it will hve yin deficiency in body",the basic pathogenesis of pulmonary fibrosis is "no need for lung",although the factors are diverse,but it is mainly composed of fluid application.Paper from the "ry win" is noval view of pathogenesis,further elaborated the pathogenesis of pulmonary fibrosis,this paper discusses the essentials of the method of treatment,for the understanding of TCM pathogenesis of pulmonary fibrosis and " nourishing Yin and replenishing Qi and at the same time invigorateing the circulation of blood" provide a theoretical basis for the application in pulmonary fibrosis.Part three:experimental research.Bleomycin is injected in a trachea to replicate rats pulmonary fibrosis model,after the model established,the next day,raise rats witht "YangfeiHuoxue Decoction".On 7 days,14 days,28 days respectively to collect peripheral blood of rats,to extract the mononuclear cells,using Westernblot to detect the PBMCs's specificity index(CD 14,NF-?Bp65,TLR4 and TGF-?)and Notch parameters(Notch1/Jagged1/CSL/DLL1),using ELISA to detect inflammatory biomarkers in plasma VEGF,IL-1? and Notch signaling pathways the three steps in the process of enzyme Furin protease and ADAM 17 and gamma secretase.The results showed that the decotion had an intervention and regulating effect on peripheral blood monocytes,especially in the early stage of inflammation.And in the later,which may affect the mononuclear cells's Notch signaling pathways Notchl/Jaggedl/the expression of CSL.The results indicate that in the early pulmonary fibrosis,YangfeiHuoxue Decoction adjusts the of inflammatory reaction,and can obstruct and relieve fibrosis formation;In the later stage,the treatment of fibrosis can be closely related to intercellular transformation and immunoregulation.All in all,the thesis use literature,theoretical and experimental research,mainly study on the pathogenesis of pulmonary fibrosis,depending on "dry win " theory,and through animal experiments,using YangfeiHuoxue Decoction intervention on the pulmonary fibrosis model,to observe the effect of the decoction of the inflammatory response in the peripheral blood mononuclear cells and the intervention of Notch signaling pathway in PBMCs in the immune response.