Effects And Mechanism Of Nerve Growth Factor On The Airway Inflammation Of Asthmatic Mice

ObjectiveTo establish the asthmatic rat model , anti-NGF was injected intraperitoneally in rat model. Investigate the pathologic changs in the lung tissues;the changs of total cell count and differential cell count in BALF;the changs of concentrations of IL-4,IFN-γand NGF in BALF;the changs of mRNA expression of IL-4,IFN-γand NGF in the lungs,so as to identify the effects and possible mechanism of NGF on the airway inflammation of asthmatic mice,and then to explore new targets in treating asthma.MethodsAdult male SD rats (n=24) were randomly divided into the control group(group A),the asthmatic group(group B),the anti-NGF group(group C),8 mice in each group.The asthmatic model was established by intraperitoneal injection of 10%OVA for sensitizing and inhalation of 1% OVA for inducing. Intraperitoneal injection and inhalation of physiologic saline to take the place of OVA diluted in PS in group A. Anti-NGF was injected intraperitoneally before inhalation of 1% OVA in group C. The pathologic changs in the lung tissues of the three groups were detected by HE staining. Extracted the BALF of the three groups,the total cell count and differential cell count in the BALF were performed. The concentrations of IL-4,IFN-γand NGF in BALF were measured by ELISA. The mRNA expression of IL-4,IFN-γand NGF in the lungs were detected by RT-PCR.Results1,The asthmatic SD rat model was established successfully.2,There were not obvious infiltration of inflammatory cells in the airways of group A;While there were obvious infiltration of inflammatory cells in the airways of group B;Compared with the group B,the airways of group C had alleviative inflammatory changes.3,The numbers of inflammtion cells,eosinophils,neutrophils and lymphocytes in BALF in group B were higher than those of the group A(P<0.05);The numbers of inflammtion cells,eosinophils,neutrophils and lymphocytes in BALF in group C were lower than those of the group B(P<0.05).4,The levels of IL-4,NGF in BALF in group B were significantly higher than those of the group A(P<0.01);while the IFN-γlevels in group B were lower than those of the group A(P<0.05);The levels of IL-4 in BALF in group C were significantly lower than those of the group B(P<0.01);while the IFN-γlevels in group C were not significantly different with that of group B(P>0.05).5,The expression of IL-4,IFN-γ,NGFmRNA in lung tissues of the three groups and the levels of IL-4,IFN-γ,NGF in BALF changed in the same way.6,The NGF levels in BALF of group B were correlated positively with the numbers of total cells,eosinophils and lymphocytes in BALF(r=0.833,0.944,0.949,P均<0.05),the concentration of IL-4 in BALF( r=0.944,P<0.01),and the mRNA of IL-4 in lung tissues(r=0.848,P<0.05),but the NGF levels in BALF of group B were not correlated with the concentration of IFN-γin BALF(r=0.122,P>0.05),and the mRNA of IFN-γin lung tissues(r=0.611,P>0.05).Conclusion1,Intraperitoneal injection of 10%OVA for sensitizing and inhalation of 1% OVA for inducing could duplicate asthmatic animal model successfully.2,The NGF may play a key role in the formation of airway inflammation in the asthmatic rats.3,Th2 is predominant T-lymphocyte in asthma,and then NGF may promote the secretion of Th2 cytokins,while the IL-4 levels increased,however NGF have no function to the the secretion of Th1 cytokins,what can further intensify the misregistration of Th1/Th2 to induce asthma.4,Anti-NGF could alleviate the airway inflammation of asthmatic mice,what may provid experimental according to explore new targets in treating asthma.