Study On The Neuro-endocrine Mechanism Of NGF Regulating The Occurrence And Development Of Allergic Rhinitis

Background:Allergic rhinitis is an inflammatory disease of the upper respiratory tract,which is essentially airway inflammation.A large number of studies have shown that allergic rhinitis mostly occurs before bronchial asthma,indicating that allergic rhinitis may further develop into bronchial asthma.Although the above-mentioned clinical phenomena are well-known,the occurrence and development of allergic rhinitis,how it evolves into bronchial asthma,and the link mechanism between allergic rhinitis and bronchial asthma,are still unclear.NGF is a polypeptide molecule that can induce the directional growth of nerve cells and promote the differentiation of nerve cells.It plays an important role in the development and differentiation of nerve cells.Studies have shown that NGF is involved in the pathogenesis of allergic rhinitis.NGF in the nasal cavity lavage fluid of allergic rhinitis rat model is significantly increased,and anti-NGF antibody instillation through the nasal cavity can effectively alleviate the local symptoms of the rat nasal cavity and reduce the pathology of the nasal mucosa Similarly,the expression of NGF in the patient’s nasal mucosal tissue and serum also has similar changes.The above shows that NGF may be involved in the pathophysiological process of airway inflammation and airway hyperresponsiveness in allergic rhinitis.This study intends to build on our work in recent years related to bronchial asthma and adrenal medullary chromaffin cells,using NGF to regulate the redundancy of asthma chromaffin cells as a starting point,from the development and differentiation of chromaffin cells and their manifestations.Beginning with the transformation of type and function,the possible mechanism of the occurrence and development of allergic rhinitis under the regulation of NGF is proposed: NGF in patients with allergic rhinitis continues to act on chromaffin cells at different stages of differentiation may gradually reduce its redundancy threshold,In order to finally break through the anti-redundant effect of glucocorticoids,pave the way for the transformation into sympathetic neurons(prone),and finally transform from the endocrine phenotype to the neuron phenotype,which in turn causes the decrease in blood adrenaline secretion,which makes it difficult to achieve relaxation The airway concentration promotes the development of allergic rhinitis into asthma.This hypothesis not only supplements and enriches the neuroendocrine pathogenesis theory of "one airway,one disease",but also may provide brand new ideas for the early prevention and treatment of allergic rhinitis and asthma.Objective:To explore the role and mechanism of NGF-induced neurogenic inflammation in allergic rhinitis(AR).Methods:1.The allergic rhinitis mice model was established by reference,and the model was identified.2.NGF and NGF high affinity receptor blocker K252 a were used to intervene allergic rhinitis mice model.3.The changes of adrenal endocrine function such as NGF,norepinephrine(NA),adrenaline(AD)concentration in serum were detected by ELISA.4.Observe the structural changes and ultrastructural changes of chromaffin cells of mice in each group with electron microscope and light microscope.5.Immunofluorescence method was used to detect the expression changes of phenylethanolamine-N-methyltransferase(PNMT)specific enzyme in mice chromaffin cells of each group.6.Western blotting is used to detect the m RNA and protein expression levels of synapse-related proteins synaptic vesicles(SYN)in chromaffin cells.Results:1.The results of he staining showed that there was no inflammatory cell infiltration in the nasal mucosa of control mice,while eosinophils and other inflammatory cells were obviously infiltrated in the nasal mucosa of AR mice,and the chromaffin cells in adrenal medulla showed different degrees of vacuolation-like changes.the adrenal medulla cells in NGF group also showed obvious vacuolation-like changes and cell edema,while the vacuolation-like changes in adrenal medulla cells in K252 a group were significantly reduced and the cell edema was not obvious.2.Immunohistochemical results showed that the expression of NGF in the lung tissue of allergic rhinitis mice model was obviously enhanced,and the expression of NGF in chromaffin cells of adrenal medulla was enhanced.3.Enzyme-linked immunosorbent assay(ELISA)was used to detect the changes of serum adrenalin and norepinephrine.Compared with the control group,the serum adrenalin concentration in model group and NGF group decreased(P<0.05),while that in K252 a group increased(P<0.05).After treatment,the concentration of norepinephrine in serum of mice in each group had no obvious change,and the difference was not statistically significant(P>0.05).4.The results of electron microscope showed that the cortical and medullary cells in the control group were arranged regularly,and the medullary cells had large cell body,clear mitochondrial structure,uniform distribution of chromaffin particles,round nucleus and smooth and clear nuclear membrane.In AR model group,the cell membrane of chromaffin nucleus in medulla was shrunk,secretory granules were loosely distributed,and cell contents disintegrated,showing apoptosis.In NGF intervention group,the cytoplasm of chromaffin cells in medulla was swollen,mitochondria were edema,and protrusions protruded.In K252 a intervention group,the gap of chromaffin cells in medulla widened,but the swelling degree of mitochondria and pathological changes decreased.5.Immunofluorescence results showed that compared with the control group,the expression of PNMT was significantly down-regulated in the model group and NGF group,while K252 a treatment could promote the expression of PNMT in the model group.6.The relative expression levels of SYN m RNA and protein in AR animal model were detected by Western blot.The results showed that the m RNA and protein levels of SYN in AR animal model were significantly higher than those in control group.Compared with model group,the m RNA and protein expression of SYN in NGF intervention model increased significantly,but compared with model group and model group +NGF group,K252 a intervention could significantly inhibit the expression level of SYN in model group.It indicated that SYN was involved in the progression of AR,and NGF could up-regulate the expression of SYN in AR model,while K252 a could inhibit the action of NGF and significantly inhibit the expression of SYN.Conclusion:NGF-induced neurogenic inflammation is involved in the occurrence and development of allergic rhinitis,and the mechanism may be related to the regulation of phenotype and functional transformation of adrenal medulla cells.