目的探讨哮喘大鼠气道重建的特征及蛋白激酶C(PKC—α)、核因子κB(NF-κB)在哮喘重建气道中的表达。方法延长卵清蛋白(OVA)激发时间制备慢性哮喘模型。36只Wistar大鼠分为6组:哮喘2、4、8周组和对照2、4、8周组,每组6只。用组织学结合图像分析系统观察各组大鼠气道炎性细胞浸润、胶原面积、平滑肌面积及杯状细胞数目等,免疫组化法观察PKC-α、NF-κB在气道的表达。结果①哮喘2、4、8周组气道壁均可见炎性细胞浸润、黏膜杯状细胞增多,与对照各组同时间点比较差异有显著性意义(P<0.05)。哮喘4、8周组大气道胶原、平滑肌面积增多,与对照4、8周组比较差异有显著性意义(P<0.05)。哮喘各组小气道胶原面积虽有增加,但无统计学意义,但哮喘8周组小气道平滑肌面积增加,与对照8周组比较差异有显著性意义(P<0.05)。②哮喘各组气道上皮细胞PKC—α、NF-κB蛋白表达增加,与对照各组同时间点比较差异有显著性意义(P<0.05)。结论通过延长OVA激发时间制备大鼠慢性哮喘模型,气道不仅存在慢性炎症,而且气道壁结构有改变,PKC—α、NF-κB可能参与哮喘的气道重建。
Objective To examine the effect of prolonged allergen exposure on airway remodeling and the expression of PKC-α and NF-κB in asthmatic rats. Methods Thirty-six Wistar rats were sensitized to ovalbumin (OVA), and then exposed to aerosolized OVA for 2, 4, 8 weeks. Number of goblet cells, the area of collagen and smooth muscle in airway were measured by means of image analysis system. The expression of PKC-α and NF-κB was detected in airway by immunohistochemistry. Resuits ①After 2, 4, 8 weeks of OVA challenge, inflammatory response and structural changes were found in airway. Compared with those in control group, goblet cells were increased. The area of collagen was significantly increased mainly in the large airways of rats after challenged to OVA for 4 and 8 weeks. Although the area of collagen in the small airways following allergen exposures was also increased compared with that in control groups, there was no statistically significant difference. The area of smooth muscle in the large airway in asthmatic groups was significantly increased as compared with that in control groups. ②Compared with those in control groups, the expression of PKC-α and NF-κB was significantly increased in airways of asthmatic groups. Conclusion Prolonged OVA exposure in sensitized rats induces chronic inflammatory and structural changes in airway. The increased expression of PKC-α and NF-κB suggested that they play a significant role in airway remodeling of asthma.