The Probing For Anti-asthma Mechanism Of Yu-ping-feng-san Based On TSLP Pathway

Asthma is a major medical problem in the world today that modern medicine is not effective thorough.Traditional Chinese medicine Yu-Ping-Feng-San(YPFS)is widely used in the clinical treatment of asthma and other allergic diseases,but its mode of action and the mechanism is not clear.Therefore,this study examines the effect of YPFS on OVA induced allergic asthma,and explored its mechanism.This study consists of three parts:Part I:The effect of YPFS on OVA-induced mouse asthmaAsthma was induced by OVA with administrating 20 ?g OVA intraperitoneally on day 0 and 14,following airway challenging by 0.5%OVA solution for 20 min from day 21 to day 28.The control group were administrated with saline.The YPFS groups were administrated intragastrically with YPFS every day and the crude drug dosage were 3.25 g·Kg-1,6.5 g·Kg-1 and 13 g·Kg-1.The model group and control group were administrated with equal volume saline.DEX was administrated intraperitoneally from day 21 to day 28 as a positive control.The results showed that the level of Eos and IgE in serum increased significantly in the model group and high level Eos was detected in BALF.Histopathological changes in lung were detected including bronchial serous exudation?tubular epithelial cells exfoliation?tube narrowing?aleveolar septum widen and lymphocytes infiltration around bronchial.While the level of Eos and IgE was reduced as compared to the model group and lung pathological changes were attenuated after treated with YPFS.PAS stainings showed that there were mucus hyper secretion in the epithelial cells in the model group while mucus secretion was lower in the 6.5 g·Kg-1 YPFS.Meanwhile,higher level of IL-4 and lower ratio of IFN-gama versus IL-4 was detected in Lung homogenates of model group.With administration of YPFS,IL-4 level in lung homogenates was reduced significantly and the ratio of IFN-gama and IL-4 was increased accordingly.Part II:The effect of YPFS on TSLP and TSLPR in the OVA-induced mouse asthmaMice were challenged 50?L of 0.5%OVA solution through their posterior pharyngeal,and then challenging by 0.5%OVA solution for 20 min from day 1 to day 3.Then YPFS groups were administrated intragastrically with YPFS 4 days advanced and also the DEX group.The results showed that the level of TSLP in BALF?Lung homogenates and airway homogenates increased significantly in the model group and also the expression of TSLPR was increased.With administration of YPFS,the level of TSLP and TSLPR are significantly reduced.Part III:Effect of YPFS on TSLP in TNF-a induced with 16HBEAfter the TNF-?(1.25?g/mL)induced with 16HBE 12 hours,the level of TSLP in the cell supernatant is significantly increased.While using YPFS and YPFS serum co-culture with 16HBE,we find YPFS serum can reduce the production of TSLP while YPFS couldn't.Through our lab's research,we find Cimicifuga and Formononetin in YPFS serum,so we co-culture 16HBE with them.The results showed that the level of TSLP were ignificantly reduced when use Cimicifuga induced 16HBE,but the production of TSLP is not defined when Formononetin co-culture?Conclusion:The results of this study implied that YPFS could attenuate OVA-induced asthma,the mechanism of YPFS may be related to inhibiting the Th2 polarization and inhibiting of the production of TSLP.