哮喘分期序贯治疗对大鼠气道重构及过敏性气道炎症的影响

Effect of staging sequential treatment for airway remodeling and allergic airway inflammation of rats

目的研究哮喘分期序贯治疗对大鼠哮喘模型气道重构及过敏性气道炎症的作用。方法 56只SD大鼠随机分成正常组、哮喘组、序贯治疗1组、序贯治疗2组、序贯治疗3组、布地奈德组、孟鲁司特钠组,每组8只,除正常组外,其余各组均以卵蛋白(OVA)辅以氢氧化铝为佐剂于第1、8、15天注射致敏,22 d后隔天雾化吸入OVA8周激发哮喘,建立哮喘模型。从实验第8天开始,给药组序贯治疗1组急性期麻杏二陈汤灌胃;序贯治疗2组急性期麻杏二陈汤灌胃,缓解期胃饲金水六君煎加减;序贯治疗3组急性期麻杏二陈汤灌胃,缓解期胃饲金水六君煎加减方,稳定期胃饲六味地黄颗粒;布地奈德组大鼠激发后雾吸沙丁胺醇,缓解期和稳定期雾吸布地奈德;孟鲁司特钠组激发后雾吸沙丁胺醇,缓解期和稳定期胃饲孟鲁司特钠;哮喘模型组以生理盐水胃饲代替,干预7周后观察实验大鼠全血白细胞总数、嗜酸性粒细胞计数,支气管平滑肌层、上皮下胶原、内管壁的厚度,肺组织羟脯氨酸含量。结果①大鼠肺支气管病理学观察表明哮喘大鼠支气管平滑肌层、上皮下胶原、内管壁厚度[(27.87±0.81)、(9.11±0.58)、(39.00±3.68)μm]均较正常组[(10.76±0.67)、(3.37±0.42)、(20.40±2.85)μm]明显增厚,肺组织羟脯氨酸含量[(11.50±3.81)mg/g]较正常组[(5.71±0.80)mg/g]明显增高,差异均有统计学意义(P=0.00),表明哮喘时存在气道重构。②序贯治疗1、2、3组、布地奈德组及孟鲁司特钠组对大鼠支气管平滑肌层、上皮下胶原、内管壁厚度、肺组织羟脯氨酸含量、全血白细胞总数及嗜酸性粒细胞计数均比哮喘模型对照组低,差异均有统计学意义(P<0.05)。结论中药分期序贯治疗具有减轻哮喘气道慢性炎症和延缓气道重构的作用。

Objective To analyze the effect of staging sequential treatment to airway remodeling and allergic airway inflammation of asthma rat models. Methods 56 male SD rats were randomly divided into group normal, group asthma, Sequential treatment group 1, 2, 3 and group Budesonide and group Montelukast, 8 rats in each group. For establishing asthma model, injection of egg ovalbumin （OVA） and aluminum hydroxide as adjuvant to the mice except for those in the normal control group were done in day 1, 8 and 15 for allergization, followed by an 8-week aerosol inhaling of OVA which started from day 22 and done once every two day as trigger of asthma. From day 8, Sequential treatment group 1 was given Ma Xing Er Chen Decoction i.g. in acute stage; sequential treatment group 2 was given Ma Xing Er Chen Decoction i.g. in acute stage and modified Jin Shui Liu Jun Decoction in remission stage; sequential treatment group 3 was given Ma Xing Er Chen Decoction i.g. in acute stage, modified Jin Shui Liu Jun Decoction by gastric gavage in remission stage and Liu Wei Di Huang Granule by gastric gavage in stable stage. Group Montelukast was given Salbutamol by aerosol inhalation at the onset of asthma and Montelukast i.g. in remission and stable stages. Group Budesonide was given Salbutamol by aerosol inhalation at the onset of asthma and Budesonide in remission and stable stages. The asthma model group was given normal saline i.g. After 7 weeks intervention, the total white blood cells, eosinophil cell count, the thickness of bronchial smooth mus- cle layer, subepithelial collagen, endotracheal tube wall, and the hydroxyproline content in lung tissue of all mice were examined. Results ①Compared with normal control group, the thickness of bronchial smooth muscle layer, subepithelial collagen, endotracheal tube wall, and the hydroxyproline content in lung tissue of asthma rats were remarkably higher [（27.87±0.81） μm vs （10.70±0.67） μm, （9.11±0.58） μm vs （3.37±0.42） μm, （39.00±3.68） μm vs （20.40±2.85） μm, （11.50±3.81） mg/g vs （5.71±0.80） mg/g, P = 0.00], which indicated the existence of airway remodeling in asthma. ②Compared with the asthma model group, the thickness of bronchial smooth muscle layer, subepithelial collagen, endotracheal tube wall, and the hydroxyproline content in lung tissue, total white blood cells and eosinophil cell count of sequential treatment group 1, 2, 3 and group Budesonide and group Montelukast were significantly lower （P 〈 0.05）. Conclusion Staging sequential treatment of Chinese medicine exerts the function of relieving chronic airway inflammation in asthma and postponing airway remodeling.