Experimental Asthma Cgrp And Ngf Role Of The Central And Peripheral Mechanism

PrefaceAsthma is characterized by airway obstruction and hyperresponsiveness. It is still not clear about the pathogenic mechanism of asthma. It has been demonstrated that the immunogenic inflammation and neurogenic inflammation might be involved in the pathogenesis of asthma.With the development of the research in asthma, the animal model of asthma has been used by many researchers. However, in our study, we have encountered many problems such as the individual differences about the reactivity of Ovalbumin inhaling as well as the best time of observing airway inflammation and airway remodeling. Our experiment is to explore the problems in preparing the asthmatic guinea pig model, which will provide more ideal experimental model for researchers.Calcitonin Gene Related Peptide (CGRP) is a polypeptide with 37 amino acids, which extensively exists in the central and peripheral nerve system. It has been demonstrated that CGRP has the function of constriction of bronchial smooth muscle, erudition of serum, secretion of mucus, which indicate that CGRP might be involved in the pathogenesis of asthma. The bodies of sensory neurons of lower respiratory tract are located at nodose ganglion and C7-T5 spinal ganglion. The central axons terminate at spinal dorsal horn and solitary nucleus. Whether any changes occurred in those areas during asthma is worth exploring.Nerve Growth Factor (NGF) belongs to the neurotrophic family, which is related to the growth, development and survives of nerve cells. Recent researches showed that NGF had more extensive biological activities, especially its roles in regulating the immune and inflammatory net are attracting the concern of many researchers. NGF is regarded as the ribbon between nerve system and immune system. It is worth exploring that whether the NGF in the lower respiratory tract and visceral afferent system of asthmatic guinea pig is involved in the pathogenesis of asthma.MethodsTo observe the relationship between different asthmatic model, time of inhaling Ovalbumin, airway reactivity, severity of asthma, severity of cough and airway inflammation and airway remodeling, the changes of the expression of CGRP in the lower respiratory tract and visceral afferent system of asthmatic guinea pigs by means of immunohistochemistry combined with micro - image a-nalysis. To observe the changes of the expression of NGF in the BALF cells of asthmatic guinea pigs and the functions of methylprednisolone sodium succinate by means of immunohistochemistry combined with micro - image analysis. To observe the changes of the expression of NGF in the lower respiratory tract and visceral afferent system of asthmatic guinea pigs by means of immunohistochemistry , in situ hybridization combined with micro - image analysis.Results1. An obvious increase in eosinophil number was observed in the bron-choalveolar lavage fluids (BALF) of asthmatic guinea pigs and the inflammation is becoming more serious with the inhaling time continue ( P <0.05). No obvious airway remodeling was observed in inhaling of Ovalbumin for 2 weeks and 4 weeks, however there is obvious airway remodeling in inhaling of Ovalbumin for 8 weeks and 12 weeks.No obvious difference was observed in eosinophil number in the BALF a-mong different reactive level of asthmatic guinea pigs after inhaling Ovalbumin ( P >0.05). With the severity of asthma, there is an obvious increase in eosinophil number in the BALF of asthmatic guinea pig (P < 0. 05 ). Comparing with the guinea pigs without cough and cough slightly, there is obvious increase in e-osinophil number in the BALF of those with serious cough (P <0. 05).2. There is slight expression of CGRP in the EOS, L and AMs of control group. The CGRP positive immureactive fibers in the control group are brownpunctate or beaded, located at airway epithelia and bronchial smooth muscles. CGRP positive immureactive cells were observed in the nodose ganglion and C7 -T5 spinal ganglion of control group. The positive reactivity are located at plasm full o...