基质金属蛋白酶-9在哮喘豚鼠气道重构中的作用及抗神经生长因子抗体干预的影响

Studies on the effects of anti-nerve growth factor antibody and expression levels of matrix metalloproteinase-9 in asthmatic guinea pig model

目的探讨哮喘豚鼠模型中基质金属蛋白酶-9(MMP-9)与气道重构的关系及抗神经生长因子抗体干预对气道重构的影响。方法重复雾化吸入卵蛋白4周建立豚鼠哮喘气道重构模型。实验分为对照组、哮喘组、抗神经生长因子(NGF)抗体干预组(每组8只豚鼠)。免疫组化方法结合显微图像分析检测MMP-9表达。半定量PCR检测MMP-9mRNA水平。结果哮喘组动物出现管壁增厚、平滑肌增生、黏液分泌增加等气道重构的特征性改变,MMP-9mRNA水平和蛋白表达均明显增高。NGF抗体组与哮喘组比较,炎症反应轻微,平滑肌增生、黏液分泌不明显,MMP-9mRNA水平和蛋白表达均降低,与对照组差异无显著性。结论少量、多次变应原吸入可导致气道重构,MMP-9在气道重构中发挥作用,NGF抗体干预可延缓气道重构的发生。

Objective To investigate the pathological features of airway remodeling and evaluate interventional ellects ol nerve growth factor （NGF） on the expression of matrix metalloproteinase-9 （MMP- 9）, an important mediator of airway remodeling, in guinea pig asthma model. Methods Guinea pigs were randomly divided into the control group, asthma group, and antibody NGF intervention group （each group had 8 guinea pigs）. In the asthma group the animals were sensitized by repeated exposure to aerosolized ovalbumin combined with AI（OH）3. The thickness of the smooth muscle of intrapulmonary bronchi was measured by image analysis system. The expression of MMP-9 in bronchi and lung tissues were assayed with immunohistochemistry combined with the mlcro-image analysis system. The levels of MMP-9 rnRNA in bronchi and lung tissues were determined by RT-PCR. Results After repeated allergen challenge, obvious infiltration of inflammatory cells and proliferation of goblet cells and smooth muscle were demonstrated in guinea pig bronchi. Expression levels of MMP-9 in the epithelial cells of bronchi were significantly higher in asthmatic animals than those of control group animals. Compared with asthmatic group, there was mild inflammation reaction, and decrease in collagen deposition and expression of MMP-9 in antibody NGF group animals, and they were not significantly higher than that in control group animals. Conclusions Repeated exposure of allergen induced airway inflammation and remodeling. MMP-9 plays an important role in airway remodeling. Antibody NGF intervention could inhibit airway remodeling through inhibition of the expression of MMP-9.