The Effect Of Aerosol Inhalation Of Anti-NGF Microspheres On The Airway Remodeling Of The Asthmatic Mice And The Mechanisms Involved

Research background and significance:Bronchial asthma(asthma)is characterized by nonspecific airway inflammation,airway hyperresponsiveness and airway remodeling.Airway remodeling is considered to be an important factor for the refractory and uncontrollable asthma.Although the fact that the represented drug by glucocorticosteroids has anti-asthma effect,which is targeted at the treatment of airway inflammation of asthma.Let the majority of patients with asthma under control.However,the pathogenesis of asthma is characterized by repeated chronic,easily changing and episodic characteristics,which indicate the complex characteristics of its occurrence mechanism.In recent years,intervention on airway remodeling has become a hot topic in asthma research.However,the mechanism of initiation and intervention is not clear.Studies have shown that never growth factor(NGF)is closely related to the airway hyperresponsiveness and airway remodeling of asthma.However,the feasibility and specific mechanism of anti-NGF treatment for asthma are not clear.Objective:On the basis of our previous work,we established an asthma airway remodeling mice model.Using various methods such as intraperitoneal injection and aerosol inhalation of anti-NGF antibodies or aerosol inhalation of slow-release microspheres,we probe into their role in the airway remodeling model of asthma mice and the possible regulatory mechanisms via TGF-and Smad signaling pathways.Methods:The airway remodeling model of asthmatic mice was established by the method of OVA sensitization and challenge.The sustained-release,safe and long-acting anti-NGF microspheres were prepared by polymer alloy method.We used various methods such as intraperitoneal injection of NGF,intraperitoneal injection of anti-NGF,aerosol inhalation of anti-NGF inhalation and aerosol inhalation of microspheres inhalation to intervene the airway remodeling model of asthmatic mice.We observed the effects of these interventions before and after intervene on airway inflammation,airway reactivity and airway remodeling.We examined NGF and TGF-?1 gene and protein expression in the airway remodeling model in asthma mice lung tissue.We further detected the expression of P-smad3,Smad7,and TGF-?1/Smad signaling pathway downstream cell marker,snail,slug,and a-SMA.Results:1.Successful establishment of chronic airway remodeling model in asthmatic mice.The airway remodeling of asthma mice was significantly reduced by intraperitoneal injection of anti-NGF antibody.The expression of NGF protein was increased on the airway epithelium in the asthma group and the NGF group.The NGF group was more obvious.Airway inflammation is significant.Intraperitoneal injection of anti-NGF antibodies can significantly inhibit lung airway inflammation in asthmatic mice and reduce collagen deposition and reticular basement membrane thickness.The expression levels of TGF-?1and P-smad3 in the anti-NGF group were significantly lower than that in the asthma group.The downstream markers of TGF-?1/Smad such as snail,slug,and a-SMA can also be inhibited by anti-NGF in bronchial epithelial cells.2.Aerosol inhalation of anti-NGF can reduce airway remodeling in asthma mice.The expression of NGF and TGF-?1 in the anti-NGF antibody group was significantly reduced.Further aerosol inhalation of anti-NGF microspheres can significantly reduce the thickness of network basement membrane,collagen deposition,airway wall thickness,NGF protein and mRNA expression level.There was a significant improvement in lung function and airway remodeling in the aerosol inhalation of anti-NGF antibody microspheres group than only single aerosol inhalation of anti-NGF.Aerosol inhalation of anti-NGF microspheres is better than pure anti-NGF.Conclusions:Aerosol inhalation of anti-NGF microspheres can significantly inhibit the airway remodeling process in asthmatic mice.The mechanism may be related to the regulation of TGF-?1/Smad signaling pathway.