基于Notch信号通路探讨金龙定喘合剂调节免疫失衡治疗哮喘的作用机制OA

Objective To explore the mechanism of Jinlong Dingchuan Mixture(金龙定喘合剂)in regulating the balance of helper T cell 17(Th17)/regulatory T cell(Treg)in the bronchial asthma mice based on Notch signaling pathway.Methods Fifty C57BL/6 mice were randomly divided into control group(control),model group(model),Jinlong Dingchuan Mixture group(JLDC),Notch agonist group(Jagged1)and Jinlong Dingchuan Mixture+Notch agonist group(JLDC+Jagged1)(n=10).The asthma model was prepared by injection and inhalation of ovalbumin(OVA).The mice in each drug group were given the corre-sponding drug by gavage/intraperitoneally once a day for 14 consecutive days.Resting minute ventilation(VE)and peak expira-tory flow rate(PEF)were measured to evaluate the lung function.HE and Masson staining methods were used to observe the pathological injury and fibrosis of lung tissue.The total cell count,eosinophils,neutrophils and lymphocytes were detected in bronchoalveolar lavage fluid(BALF).Flow cytometry was used to determine the proportion of helper T cells 17(Th17)and regu-latory T cells(Treg)in peripheral blood.The levels of interleukin(IL)-10,IL-17 and transforming growth factor-β(TGF-β)in bronchoalveolar lavage fluid(BALF)were measured,and the expressions of Notch1 and Hes1 protein in lung tissue were detected.Results The lung function of JLDC group was significantly improved,and the pathological injury and fibrosis of the lung tissue were significantly alleviated.The number of inflammatory cells in BALF decreased significantly.Th17/Treg ratio was sig-nificantly decreased,the levels of IL-10 and TGF-β were significantly increased,and IL-17 levels were significantly de-creased.The expression levels of Notch1 and Hes1 were significantly decreased.Notch agonist Jagged1 can partially reverse the above therapeutic effects of Jinlong Dingchuan Mixture on the asthmatic mice.Conclusion Jinlong Dingchuan Mixture can im-prove Th17/Treg balance,inhibit inflammatory response and improve lung function in the mice with tracheal asthma,and its mechanism may be related to inhibiting Notch signaling pathway.