Pharmacodynamic Evaluation And Mechanism Study Of Shenqi Biyan Granule In The Treatment Of Allergic Rhinitis

Allergic rhinitis(AR)is a common chronic inflammatory disease,which is characterized by pathological changes of nasal mucosa.In recent years,AR is affecting more and more people with the increasing kinds of allergen.Epidemiological data indicate that AR affects up to 10%-15%of the global population and afflicts more than 35%of people in China.AR an immunological disorder is caused by genetic and environmental factors.In allergic subjects,persistent or repetitive exposure to allergens that typically are substance common in the environment,leads to chronic allergic inflammation which significantly impedes patient quality life and work performance.Current therapeutic drugs towards AR can only alleviate allergic symptoms but fail to regulate the allergic reaction and bring adverse effects,however,traditional Chinese medicine have advantage of immmunoregulatory effects for its bioactive compounds and multi-target combination.Consequently,researching and developing safe and effective herbal medicine according to the pathogenesis of AR is necessary.AR belongs to Bei Qiu in the Traditional Medicine of China(TCM).which is related to specific mechanism disorder.Shenqi,a traditional Chinese polyherbal medicine composed of Angelica dahurica(Fisch.exHoffm.)Benth.et Hook.f.,Scutellaria baicalensis Georgi.Lonicera japonica Thunb.,Mentha haplocalyx Briq.,Astragalus membranaceus(Fisch.)Bunge.Codonopsis tangshen Oliv.,Isatis indigotica Fort.,TaraxacMm mongolicum Hand.-Mazz.,Agrimonia pilosa Ledeb.and Asarum sieboldii Miq.has been widely used in the clinical treatment of AR in Xinjiang and exhibited anti-AR effects.Shenqi was prepared according to original prescription for the treatment of AR.This thesis aims to investigate the role of Shenqi for the treatment of AR rats and explore the possible mechanisms of Shenqi for anti-allergic activity.OVA-induced AR rat model was built to evaluate the therapeutic effect of Shenqi.The potential anti-allegic rhinitis mechanism was also investigated,including its anti-allergic effect on IgE-induced mast cell degranulation and its immunoregulatory effect on OVA-induced primary spleen lymphocytes differentiation.Our research will provide an experimental evidence and theoretical basis for clinical therapy of Shenqi in AR.Chapter 1 The study of therapy effects of Shenqi for AR ratsIn our study,OVA-induced AR rat model was used to evaluate the therapy effects of Shenqi.The results showed that Shenqi could remarkably alleviate the AR symptoms.the morphological changes of nasal mucosa,and the IgE production in OVA-sensitized rats.Otherwise,Shenqi could regulate the balance between Thl cytokine IFN-y and Th2 cytokin IL-4 which demonstrated that Shenqi had treatment effect on AR by regulating the balance of Th1/Th2.Chapter 2 Anti-allergic effects of ShenqiMast cell degranulation and the production of inflammatory mediators are important inducers for allergic reaction.The study used IgE to sensitize RBL-2H3 cells to investigate the influence of Shenqi on mast cell degranulation.The results indicated that Shenqi mightbe acting on suppressing mast degranulation thus plays anti-allergic effects.Chapter 3 The immunoregulatory effects of ShenqiT helper cells activated by antigens will differentiate into two functionally distinct subsets that cross-regulate each other by secreting different cytokines.Once the balance between Thl and Th2representing cytokine is broken and dysregulation of Th2 cytokine can lead to AR.In this part,we used primary lymphocyte cells to observe the role of Shenqi for the secretion of Th1 and Th2 cytokine and the expression of Th1 and Th2 transcription factors.The results showed that Shenqi could improve the imbalance of IFN-?/IL-4 and T-bet/GATA3 which are related to the differentiation of Th1 or Th2 and markedly inhibit the expression of SOCS1 and p-STAT6.This suggested that Shenqi executed anti-allergic effects probably act through improvement of Thl/Th2 balance.In summary,this thesis focused on evaluating the anti-allergic effects of Shenqi on AR rat model and exploring the potential mechanism including anti-allergic activity and immunoregulatory effect.It may provide an experimental basis on noval anti-allergic drugs for the treatment of AR.