抗神经生长因子局部植入在哮喘发病中的作用  

The Role of Local Embedding Intervention of Anti-nerve Growth Factor Microspheres in Pathogenesis of Asthma

作　　者：李园园[1] 胡成平[1] 冯俊涛[1] 谷海刚[2] 邓彭博[1] 王胜峰[3] 贺若曦[1] 

机构地区：[1]中南大学湘雅医院呼吸内科,湖南长沙410008 [2]美国佐治亚州亚特兰大埃默里大学医学院麻醉学系 [3]中南大学湘雅三医院药剂科,湖南长沙410013

出　　处：《中国呼吸与危重监护杂志》2013年第3期293-299,共7页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：中央高校基本科研业务费专项资金资助(编号:2011QNZT146)

摘　　要：目的将神经生长因子(NGF)缓释微球和抗NGF缓释微球局部植入哮喘大鼠肾上腺,探讨抗NGF在哮喘发病中的可能作用机制。方法雄性SD大鼠32只,随机分为对照组、哮喘组、NGF干预组和抗NGF干预组,分别干预后予行为学、肺功能、肺组织切片HE染色、肾上腺髓质细胞超微结构(电镜)、肾上腺组织中NGF和苯乙醇胺N-甲基转移酶(PNMT)表达(免疫组织化学法)、血清中NGF、皮质醇、皮质酮、肾上腺素、去甲肾上腺素的浓度(ELISA法)检测。结果行为学示哮喘组大鼠均有不同程度喘鸣、搔抓、烦躁、大小便失禁、攻击性增强等行为,抗NGF组症状相对较轻。肺功能检测示哮喘组、抗NGF、NGF组大鼠均存在气道高反应,抗NGF组较哮喘组气道阻力降低,动态肺顺应性升高。肺组织HE染色示哮喘组存在支气管收缩、炎症细胞浸润、支气管上皮细胞脱落,抗NGF组上述征象不明显。电镜观察见哮喘组、NGF组肾上腺髓质细胞出现空泡样变,嗜铬颗粒分布不均,数量和浓度较对照组降低;NGF组肾上腺髓质细胞膜可见突起;抗NGF组基本接近正常组。抗NGF组PNMT和NGF平均灰度值与哮喘组相比均有明显差异。各组间不同指标浓度水平:(1)肾上腺素:对照组>抗NGF组>哮喘组>NGF组;(2)去甲肾上腺素:NGF组>哮喘组>抗NGF组>对照组;(3)皮质醇:无显著差异;(4)皮质酮:对照组>抗NGF组>哮喘组>NGF组。结论局部植入抗NGF微球能减轻哮喘大鼠肺组织炎性细胞浸润、改善肺功能。其作用机制可能为抗NGF逆转了NGF启动的肾上腺髓质细胞转分化过程。Objective Using nerve growth factor （NGF） and anti-NGF microspheres injected directly into the asthmatic rat adrenal gland, to explore the possible role of anti-NGF microsphere treatment in asthma. Methods 32 male SD rats were randomly divided into a normal control group, an asthma group, a NGF microspheres group, and an anti-NGF microspheres group. The behavior of rats, lung function testing, light microscopy of lung biopsy, electron microscopy of adrenal medulla cell uhrastructure changes, NGF and phenylethanolamine N-methyhransferase （PNMT） expressions in the adrenal gland were assayed by immunohistochemistry method, and serum NGF, cortisol, corticosterone, epinephrine and norepinephrine concentrations were detected by ELISA. Results Behavior in the asthma rats showed varying degrees of sneezing, runny nose, wheezing, scratching the head and face, irritability holes, incontinence, increased aggression and other acts, while in the anti-NGF rats showed relatively slighter symptoms. The rats in the asthma,anti-NGF and NGF groups showed significant airway hyperresponsiveness, while RL value reduced and Cdyn value increased in the anti-NGF group compared with the asthma group. HE staining of lung tissue revealed obvious bronchoconstriction, inflammatory cell infiltration around small vessels and alveolar spaces and in interstitum, bronchial epithelial cells desquamation in the asthma group. In anti-NGF group, trachealepithelium was relatively complete, inflammatory exudation, bronchoconstriction and inflammatory cell infiltration were milder compared to the asthma group. Electron microscopy showed vaeuolated changes of adrenal medulla cells, uneven distribution of chromaffin granules in the asthma group and the NGF group, and the quantity and concentration of chromaffin granules were significantly lower than normal. There were villous clubbing processes on the adrenal medulla cell membrane in the NGF group. While the anti-NGF group had no significant vacuolar changes in chromaffin granules and the concentra

关 键 词：哮喘 神经生长因子 抗神经生长因子 肺功能 肾上腺素 皮质酮 

分 类 号：R562.25[医药卫生—呼吸系统]