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目的:研究脑源性神经营养因子(BDNF)在豚鼠咳嗽变异性哮喘(CVA)发生发展中的调控机制和对生长相关蛋白43(GAP-43)表达的影响。方法:选择Hartley雄性豚鼠为研究对象,制备并鉴定CVA豚鼠模型,确定CVA发作时脑内BDNF含量和(GAP-43)表达的变化。人为改变CVA豚鼠中枢BDNF含量,观察外周气道炎症和中枢GAP-43表达的相应改变。结果:制备的CVA豚鼠模型通过鉴定符合要求。(1)模型组豚鼠中枢BDNF和GAP-43表达量明显高于生理盐水对照组(P<0.05)。(2)与中枢注射人工脑脊液的CVA豚鼠相比,注射外源性BDNF可以增加肺组织气道周围的物质P免疫阳性反应物并加剧外周气道炎症,同时中枢GAP-43免疫阳性反应物分布增多(154.3±25.7 vs 78.2±22.8,P<0.01)。结论:中枢BDNF在豚鼠CVA发生发展中具有调控作用,这种作用可能通过调节GAP-43表达产生。
AIM: To investigate the regulatory mechanism of brain derived neurotrophic factor (BDNF) in the development and progression of guinea pig cough variant asthma (CVA) and its effect on the expression of growth-associated protein 43 (GAP-43). Methods: Hartley male guinea pigs were selected as the experimental subjects. CVA guinea pig models were prepared and identified to determine the changes of BDNF content and (GAP-43) expression in CVA. The contents of BDNF in CVA guinea pig were artificially changed, and the corresponding changes of peripheral airway inflammation and central GAP-43 expression were observed. Results: The CVA guinea pig model was identified to meet the requirements. (1) The expression of BDNF and GAP-43 in guinea pigs in model group was significantly higher than that in saline control group (P <0.05). (2) Compared with CVA guinea pig injected with artificial cerebrospinal fluid (CSF), the exogenous BDNF could increase P-positive immunoreactive substances around the airway of lung tissue and exacerbate peripheral airway inflammation, meanwhile, distribution of central GAP-43 immunoreactive reactant (154.3 ± 25.7 vs 78.2 ± 22.8, P <0.01). CONCLUSION: Central BDNF plays a regulatory role in the development of CVA in guinea pigs, and this effect may be caused by the regulation of GAP-43 expression.